Early white matter involvement in an infant carrying a novel mutation in ACOX1.

We describe the clinical findings and MRI features observed in a child who presented a two-step disease course: he was hypotonic at birth and soon afterwards developed seizures, which were partially responsive to treatment; he subsequently showed developmental delay and a progressive neurological deterioration with the onset of severe seizures at around three years of age. Head MRI at age 20 days was unremarkable, whereas at 25 months it showed bilateral hyperintensity of the deep cerebellar nuclei; five months later, the signal hyperintensity was also present in the cerebellar white matter and ventral pontine fibre tracts. Molecular analysis revealed a novel ACOX1 mutation, predicting a largely truncated protein. The white matter involvement, which followed an ascending trajectory from cerebellar and brainstem structures to the cerebral hemispheres, seemed to originate from the perinuclear white matter of the deep cerebellar nuclei.

Schizophrenia severity, social functioning and hippocampal neuroanatomy: three-dimensional mapping study.

BACKGROUND: Hippocampal shrinkage is commonly reported in schizophrenia, but its role in the illness is still poorly understood. In particular, it is unclear how clinical and psychosocial variables relate to hippocampal volumes. AIMS: To investigate neuroanatomic differences in the hippocampus using three-dimensional (3D) computational image analysis. METHOD: We used high-resolution magnetic resonance imaging and surface-based modelling to map the 3D profile of hippocampal differences in adults with schizophrenia (n = 67) and a healthy control group (n = 72). Manual tracings were used to create 3D parametric mesh models of the hippocampus. Regression models were used to relate diagnostic measures to maps of radial distance, and colour-coded maps were generated to show the profile of associations. RESULTS: There was no detectable difference between the schizophrenia and control groups in hippocampal radial distance. In the schizophrenia group, however, bilateral shape deflation was associated with greater illness severity (length of illness, positive and negative symptoms) and with poorer social functioning (educational level, quality of life and health status), which survived Bonferroni correction. CONCLUSIONS: Illness severity and poor social functioning may be associated with hippocampal deflation in schizophrenia. As a structural sign of poor outcome, imaging measures might help to identify a subgroup of patients who may need specific treatment to resist hippocampal shrinkage, such as cognitive rehabilitation or physical exercise.

Congenital aural atresia treated with floating mass transducer on the round window: 5 years of imaging experience.

PURPOSE: The aim of this paper is to illustrate imaging features of patients affected by congenital aural atresia (CAA) before and after treatment with a Vibrant SoundBridge (VSB) device implanted on the round window. MATERIALS AND METHODS: Ten patients (5 males and 5 females; mean age 22.1 years) with CAA underwent preoperative high-resolution computed tomography (HRCT) to estimate the degree of involvement of the middle- and inner-ear structures and highlight radiological landmarks useful for surgical planning. RESULTS: Bilateral CAA, mostly of the mixed type, was present in 7 patients and ossicular chain abnormalities in 16 ears (94% of cases). The round window region was normal in all patients, whereas facial-nerve course and/or caliber abnormalities were present in 6 ears (35.3%). The tympanic cavity was small in 13 ears (76.5%), whereas the mastoid was well pneumatized in 8/17 (47%). CONCLUSIONS: HRCT provides accurate information about anatomy and malformations of the middle and inner ear and can thus assist the surgeon in planning the procedure.

Altered microstructure integrity of the amygdala in schizophrenia: a bimodal MRI and DWI study.

BACKGROUND: The amygdala plays a central role in the fronto-limbic network involved in the processing of emotions. Structural and functional abnormalities of the amygdala have recently been found in schizophrenia, although there are still contradictory results about its reduced or preserved volumes. METHOD: In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed structural magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI), exploring amygdalar volume and microstructural changes in 69 patients with schizophrenia and 72 matched healthy subjects, relating these indices to psychopathological measures. RESULTS: Measuring water diffusivity, the apparent diffusion coefficients (ADCs) for the right amygdala were found to be significantly greater in patients with schizophrenia compared with healthy controls, with a trend for abnormally reduced volumes. Also, significant correlations between mood symptoms and amygdalar volumes were found in schizophrenia. CONCLUSIONS: We therefore provide evidence that schizophrenia is associated with disrupted tissue organization of the right amygdala, despite partially preserved size, which may ultimately lead to abnormal emotional processing in schizophrenia. This result confirms the major role of the amygdala in the pathophysiology of schizophrenia and is discussed with respect to amygdalar structural and functional abnormalities found in patients suffering from this illness.

Cerebral distribution of white matter lesions in migraine with aura patients.

OBJECTIVE: The objective of the study was to compare the cerebral distribution of white matter lesions (WMLs) between migraine patients with different aura symptoms. METHODS: Migraine with aura (MA) patients were consecutively enrolled as part of the Shunt-Associated Migraine (SAM) study. According to clinical symptoms, aura was classified as motor, aphasic, sensory, visual or vertebrobasilar. Standard and FLAIR (fluid attenuated inversion recovery) T(2)-weighted MRI sequences were inspected for WMLs by three independent raters blinded to clinical data. WMLs were assessed in the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white matter (D-WMLs) with the Schelten's scale. Interobserver agreement was good to excellent (k = 0.64 to 0.96, p < .0001). RESULTS: One hundred and eighty-five patients (77% women) were included. Aura symptoms were classified as visual in 172 (99%) patients, sensory in 76 (42%), aphasic in 54 (30%), motor in 39 (21%) and vertebrobasilar in 17 (9%) patients. One hundred and four patients (57%) exhibited more than one type of aura. D-WMLs were mainly detected in the frontal lobes (86%). There was no association between type of aura and the presence of WMLs in any cerebral location. CONCLUSION: Aura symptoms do not influence the cerebral distribution of WMLs associated with migraine disease.

Radiation dose saving through the use of cone-beam CT in hearing-impaired patients.

PURPOSE: Bionic ear implants provide a solution for deafness. Patients treated with these hearing devices are often children who require close follow-up with frequent functional and radiological examinations; in particular, multislice computed tomography (MSCT). Dental volumetric cone-beam CT (CBCT) has been reported as a reliable technique for acquiring images of the temporal bone while delivering low radiation doses and containing costs. The aim of this study was to assess, in terms of radiation dose and image quality, the possibility of using CBCT as an alternative to MSCT in patients with bionic ear implants. MATERIALS AND METHODS: One hundred patients (mean age 26 years, range 7-43) with Vibrant SoundBridge implants on the round window underwent follow-up: 85 with CBCT and 15 with MSCT. We measured the average tissue-absorbed doses during both MSCT and CBCT scans. Each scan was focused on the temporal bone with the smallest field of view and a low-dose protocol. In order to estimate image quality, we obtained data about slice thickness, high- and low-contrast resolution, uniformity and noise by using an AAPM CT performance phantom. RESULTS: Although the CBCT images were qualitatively inferior to those of MSCT, they were sufficiently diagnostic to allow evaluation of the position of the implants. The effective dose of MSCT was almost three times higher than that of CBCT. CONCLUSIONS: Owing to low radiation dose and sufficient image quality, CBCT could be considered an adequate technique for postoperative imaging and follow-up of patients with bionic ear implants.

Right-to-left shunt does not increase white matter lesion load in migraine with aura patients.

BACKGROUND: White matter lesions (WMLs) are commonly found on brain MRI of migraine patients. Migraine with aura (MA+) is associated with an increased frequency of right-to-left shunt (RLS) mostly due to patent foramen ovale. The relationship between WML load and RLS in MA+ is currently unknown. METHODS: MA+ patients were consecutively enrolled as part of the Shunt Associated Migraine (SAM) study. Patients underwent a standardized headache and vascular risk factors questionnaire, contrast-enhanced transcranial Doppler, blood coagulation tests, and brain MRI. RLS was categorized into four grades: no shunt, <10 microbubbles (mb), >10 mb single spikes pattern, and >10 mb shower/curtain pattern. Standard and fluid-attenuated inversion recovery T2-weighted MRI sequences were inspected for WMLs by three independent raters blinded to RLS grade. WML load was scored in the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white matter (D-WMLs) with the Scheltens scale. Interobserver agreement was good to excellent (kappa = 0.64 to 0.96, p < 0.0001). WML load was then correlated between patients with and without RLS. RESULTS: One hundred eighty-five patients (77% women) were included. PV-WML load was similar between patients with and without RLS. D-WML load decreased in patients with RLS (p = 0.045). On logistic regression analysis, only age was associated with WMLs (p < 0.001). CONCLUSIONS: The presence of right-to-left shunt does not increase white matter lesion load in patients who have migraine with aura.

Bionic ear imaging.

PURPOSE: The aim of this study was to illustrate the different imaging features of middle and inner ear implants, brainstem implants and inferior colliculus implants. MATERIALS AND METHODS: We retrospectively reviewed the computed tomography (CT) images of 468 patients with congenital or acquired transmissive or neurosensory hearing loss who underwent surgery. The implants examined were: 22 Vibrant Soundbridge implants, 5 at the long limb of the incus and 17 at the round window, 350 cochlear implants, 95 brainstem implants and 1 implant at the inferior colliculus. All patients underwent a postoperative CT scan (single or multislice scanner) and/or a Dentomaxillofacial cone-beam CT scan (CBCT) (axial and multiplanar reconstruction), and/or a plain-film radiography to visualise the correct position of the implant. RESULTS: The CBCT scan depicts Vibrant site of implant better than plain-film radiography, with a lower radiation dose compared to CT. For cochlear implants, a single plain radiograph in the Stenvers projection can directly visualise the electrodes in the cochlea. All patients with brainstem or inferior colliculus implants underwent postoperative CT to exclude complications and the assess correct implantation, but the follow-up of these implants can be performed by plain radiography alone. CONCLUSIONS: CT and CBCT scans are reliable and relatively fast methods for precisely determining the location of middle ear implants. CBCT is preferable to CT because of the lower radiation dose administered; a single plain-film radiograph is enough to visualise and follow-up cochlear, brainstem and inferior colliculus implants.

Increased fronto-temporal perfusion in bipolar disorder.

OBJECTIVES: Previous imaging reports showed over-activation of fronto-limbic structures in bipolar patients, particularly in response to emotional stimuli. In this study, for the first time, we used perfusion weighted imaging (PWI) to analyze lobar cerebral blood volume (CBV) in bipolar disorder to further explore the vascular component to its pathophysiology. METHODS: Fourteen patients with DSM-IV bipolar disorder (mean age+/-SD=49.00+/-12.30 years; 6 males, 8 females) and 29 normal controls (mean age+/-SD=45.07+/-10.30 years; 13 males, 16 females) were studied. PWI images were obtained following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), with a 1.5 T Siemens magnet using an echo-planar sequence. The contrast of enhancement (CE), was calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/So*100) for frontal, temporal, parietal, and occipital lobes, bilaterally, on two axial images. Higher CE values correspond to lower CBV and viceversa. RESULTS: Bipolar patients had significantly lower CE values in left frontal and temporal lobes (p=0.01 and p=0.03, respectively) and significantly inverse laterality index for frontal lobe (p=0.017) compared to normal controls. No significant correlations between CE measure and age or clinical variables were found (p>0.05). CONCLUSION: This study found increased left frontal and temporal CBV in bipolar disorder. Fronto-temporal hyper-perfusion may sustain over-activation of these structures during emotion modulation, which have been observed in patients with bipolar illness.

Continuous EEG-fMRI in Pre-Surgical Evaluation of a Patient with Symptomatic Seizures: Bold Activation Linked to Interictal Epileptic Discharges Caused by Cavernoma.

We used continuous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) to identify the linkage between the "epileptogenic" and the "irritative" area in a patient with symptomatic epilepsy (cavernoma, previously diagnosed and surgically treated), i.e. a patient with a well known "epileptogenic area", and to increase the possibility of a non invasive pre-surgical evaluation of drug-resistant epilepsies. A compatible MRI system was used (EEG with 29 scalp electrodes and two electrodes for ECG and EMG) and signals were recorded with a 1.5 Tesla MRI scanner. After the recording session and MRI artifact removal, EEG data were analyzed offline and used as paradigms in fMRI study. Activation (EEG sequences with interictal slow-spiked-wave activity) and rest (sequences of normal EEG) conditions were compared to identify the potential resulting focal increase in BOLD signal and to consider if this is spatially linked to the interictal focus used as a paradigm and to the lesion. We noted an increase in the BOLD signal in the left neocortical temporal region, laterally and posteriorly to the poro-encephalic cavity (residual of cavernoma previously removed), that is around the "epileptogenic area". In our study "epileptogenic" and "irritative" areas were connected with each other. Combined EEG-fMRI may become routine in clinical practice for a better identification of an irritative and lesional focus in patients with symptomatic drug-resistant epilepsy.

Effect of a Static Magnetic Field (1.5T) on Brain Oscillatory Activities in Resting State Condition.

The aim of the present study was to compare the EEG signal recorded outside and inside a 1.5T magnetic resonance (MR) scanner. The EEG was recorded in eyes open and eyes closed conditions using a digital recording MR-compatible system. To characterize how a static magnetic field induces changes in EEG signal, EEG data were analyzed using FFT frequency analysis. No significant difference between the alpha powers recorded outside and inside the magnetic field was observed in eyes closed conditions. However, in eyes open condition there was a significant increase in alpha power inside the magnet in comparison to the outside position. The changes in alpha power according to the eyes open/closed conditions could be inversely correlated to a subject's state of wakefulness and due to some physiological changes, rather than an effect of the magnetic field. This experiment suggests that subjects' state of wakefulness is of prime concern when performing functional MRI.

A case of pegylated interferon alpha-related diabetic ketoacidosis: can this complication be avoided?

We report the case of a 42-year-old woman with chronic hepatitis C (genotype 1), who in June 2004 started therapy with pegylated interferon alpha (PEG-IFNalpha) plus ribavirin. Two months later, she discontinued treatment because of polydipsia, polyuria and vomiting leading to a marked dehydration. Biochemical data showed type 1 diabetes mellitus with ketoacidosis, and insulin therapy was started. The patient, who before starting PEG-IFN alpha plus ribavirin therapy tested negative for glutamic acid decarboxylase antibodies (GADAb) and islet cell (ICAb) antibodies, became strongly positive for both autoimmune markers. This case confirms that patients with chronic hepatitis C who do not have baseline markers of pancreatic autoimmunity may develop severe ketoacidosis during treatment with PEG-IFNalpha, as well as with standard IFNalpha. In order to avoid this complication, as no guidelines are available and the pancreatic autoimmunity markers are not routinely analysed, we suggest frequent monitoring (e.g., every one to two weeks) of glycaemic values: e.g., every one to two weeks during the first 3 months (when this complication occurs most frequently) and monthly thereafter so as to identify diabetes at an early stage and before the onset of the appearance of severe ketoacidosis, which is life-threatening.

Cortical white-matter microstructure in schizophrenia. Diffusion imaging study.

BACKGROUND: Several, although not all, of the previous small diffusion-weighted imaging (DWI) studies have shown cortical white-matter disruption in schizophrenia. AIMS: To investigate cortical white-matter microstructure with DWI in a large community-based sample of people with schizophrenia. METHOD: Sixty-eight people with schizophrenia and 64 healthy controls underwent a session of DWI to obtain the apparent diffusion coefficient (ADC) of white-matter water molecules. Regions of interest were placed in cortical lobes. RESULTS: Compared with controls, the schizophrenia group had significantly greater ADCs in frontal, temporal and occipital white matter (analysis of covariance, P < 0.05). CONCLUSIONS: Our findings confirm the presence of cortical white-matter microstructure disruption in frontal and temporo-occipital lobes in the largest sample of people with schizophrenia thus for studied with this technique. Future brain imaging studies, together with genetic investigations, should further explore white-matter integrity and genes encoding myelin-related protein expression in people with first-episode schizophrenia and those at high risk of developing the disorder.

Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease.

BACKGROUND: Recently, mutations affecting different domains of dynamin-2 (DNM2) were associated alternatively with autosomal dominant centronuclear myopathy or dominant intermediate (demyelinating and axonal) Charcot-Marie-Tooth disease (CMT) type B. OBJECTIVE: To assess the etiologic role of DNM2 in CMT. METHODS: We performed a mutational screening of DNM2 exons 13 through 16 encoding the pleckstrin homology domain in a large series of CMT patients with a broad range of nerve conduction velocities and without mutations in more common genes. RESULTS: We identified two novel DNM2 mutations that cosegregated with purely axonal CMT in two pedigrees without clinical evidence of primary myopathy. CONCLUSION: Patients with axonal Charcot-Marie-Tooth disease type 2 neuropathy without mutations in more common genes should undergo investigation for DNM2 pleckstrin homology.

Role of CT and MRI in the preoperative evaluation of auditory brainstem implantation in patients with congenital inner ear pathology.

PURPOSE: The purpose of this study was to evaluate the reliability of computed tomography (CT) and magnetic resonance imaging (MRI) in characterising cochlear nerve anomalies in auditory brainstem implant candidates with congenital hearing loss. MATERIALS AND METHODS: Seventeen patients affected by congenital sensorineural hearing loss were examined by CT and MRI. Inner ear malformations eligible for auditory brainstem implants were classified according to the Casselman classification. All patients subsequently received auditory brainstem implants. RESULTS: Suspected congenital anomalies were confirmed by CT and MRI in all 17 patients. There were 5/17 bilateral cochlear nerve aplasias and 12/17 cochleovestibular anomalies. Of these, 5/12 patients had a common cochleovestibular cavity, 2/12 had bilateral cochlear aplasia and cochlear nerve agenesis, 1/12 had type I incomplete partition, 2/12 had type II incomplete partition and 2/12 had cochlear hypoplasia. CONCLUSIONS: Preoperative CT and MRI assessment of patients with sensorineural hearing loss is reliable. MRI provided additional information, identifying the possible absence of cochlear nerve and excluding other central nervous system (CNS) diseases.

Myasthenia gravis during low-dose IFN-alpha therapy for chronic hepatitis C.

We describe the case of a 56-year-old man who had high aminotransferase levels and anti-hepatitis C virus (HCV) antibodies. He underwent liver biopsy and biochemical screening to evaluate whether he would benefit from interferon (IFN) treatment. The patient was discharged with a diagnosis of HCV-related active chronic hepatitis, skin porphyria, and type 2 diabetes. On December 5, 1995, he began therapy with recombinant IFN-alpha at a dose of 3 MIU three times a week. He stopped this therapy in February 1996 because of asthenia, diplopia, headache, and anxiety. During IFN therapy, he had normal aminotransferase levels and no detectable HCV RNA, a condition that persists to the present. Between March and May 1996, the patient was admitted several times to a neurology clinic, where myasthenia gravis was diagnosed and treatment with pyridostigmine and cyclosporine was initiated. This case and others indicate that caution should be exercised in administering IFN because low doses can be correlated with myasthenia gravis in patients without malignancies.

Multivariate discriminant function based on six biochemical markers in blood can predict the cirrhotic evolution of chronic hepatitis.

BACKGROUND: Serologic markers have been proposed for monitoring hepatic fibrosis in chronic active liver disease. Because none of these markers, when used singly, is totally satisfactory, we developed and evaluated a multivariate approach. METHODS: We studied two cohorts of chronic hepatitis (54 patients) and cirrhosis patients (49 patients) to identify a panel of biochemical markers that discriminates between the two diseases. Using multivariate discriminant analysis, we selected a function, based on the concentrations of six biochemical markers (fibronectin, prothrombin, pseudocholinesterase, alanine aminotransferase, manganese superoxide dismutase, and N-acetyl-beta-glucosaminidase). We then prospectively validated this function on a second temporal cohort of patients. RESULTS: Multivariate discriminant analysis correctly classified 93.7% of patients (94.3% of chronic hepatitis and 92.9% of cirrhosis patients) in the first cohort and 85% of patients (89.5% of chronic hepatitis patients and 81% of cirrhosis patients) in the second cohort. CONCLUSIONS: Discriminant analysis of results of six inexpensive biochemical markers provides a high predictive value for differentiation between liver cirrhosis and chronic hepatitis. Consequently, these biochemical markers condensed into a multivariate discriminant analysis value for each patient provide information that can be contributory for subsequent options during the evolution of the natural history of chronic hepatitis.

A case of paracoccidioidomycosis: experience with long-term therapy.

We describe long-term therapy for paracoccidioidomycosis occurring in a 61-year-old house-painter from Venezuela. The diagnostic examinations made in South America had shown pulmonary granulomatous lesions and an osteolytic pattern of the left knee that had been considered suspect of malignant disease with an indication for limb amputation. With the aid of fine needle aspiration biopsy (FNAB) and culture examination we diagnosed an osteomyelitis by Paracoccidioides brasiliensis and initiated therapy with itraconazole, 400 mg per day, reduced to 200 mg per day after 2 months. At the end of 2 years of drug therapy, we observed complete regression of the pulmonary lesions and of the osteolytic area of the left knee. Moreover, we have periodically observed our patient to verify his clinical development and he is still in good health. We suggest that this pathology be considered in differential diagnosis of leprosy, tuberculosis, leishmaniasis, and systemic mycoses, even in non-endemic areas.

Fossa navicularis magna.

A notchlike bone defect in the basiocciput due to a prominent fossa navicularis was incidentally discovered in a patient referred for radiologic evaluation of sinusitis. MR images showed that the osseous defect was filled with lymphoid tissue of the pharyngeal tonsil. The occurrence of this anatomic variant is discussed, with reference to ancient anatomic works.