Mladen Bjelan

Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant

The early presentation of autonomic dysfunctions at the disease onset has been considered the mandatory clinical feature in adult-onset autosomal dominant leukodystrophy, which is a rarely recognised leukodystrophy caused by duplication of the lamin B1 gene. We report the first family with adult-onset autosomal dominant leukodystrophy and lamin B1 duplication, without the distinguishing early-appearing autonomic dysfunctions. Subjects from three consecutive generations of a multi-generational Serbian family affected by adult-onset autosomal dominant leukodystrophy underwent clinical, biochemical, neurophysiological, neuroradiological, and genetic studies. The patients atypically exhibited late autonomic dysfunctions commencing at the disease end-stages in some. Genetic findings of lamin B1 duplication verified adult-onset autosomal dominant leukodystrophy, which was supported also by neuroimaging studies. Exclusively, proton magnetic spectroscopy of the brain revealed a possibility of neuro-axonal damage in the white matter lesions, while magnetic resonance imaging of the spinal cord excluded spinal myelin affection as a required finding in this leukodystrophy. The detection of lamin B1 duplication, even when autonomic dysfunctions do not precede the other symptoms of the disease, proves for the first time that lamin B1-duplicated adult-onset autosomal dominant leukodystrophy may have a phenotypic variant with delayed autonomic dysfunctions. Prior to this report, such a phenotype had been speculated to represent an entity different from lamin B1-duplicated leukodystrophy. Hereby we confirm the underlying role of lamin B1 duplication, regardless of the autonomic malfunction onset in this disorder. It is the only report on adult-onset autosomal dominant leukodystrophy from Southeastern Europe.

Proton Chemical Shift Imaging Study of the Combined Antiretroviral Therapy Impact on Neurometabolic Parameters in Chronic HIV Infection

BACKGROUND AND PURPOSE: The introduction of combination antiretroviral therapy has failed to reduce the high prevalence of mild forms of HIV-associated neurocognitive disorders. The aim of this study was to test the effect of combined antiretroviral therapy on brain metabolite ratios in chronic HIV infection by using proton chemical shift imaging. MATERIALS AND METHODS: We performed 2D chemical shift imaging in 91 subjects (31 HIV+ patients with chronic infection on combination antiretroviral therapy, 19 combination antiretroviral therapy–naïve HIV+ subjects with chronic infection, and 41 healthy controls), covering frontal and parietal subcortical white and cingulate gyrus gray matter, analyzing ratios of NAA/Cr and Cho/Cr on long-TE and mIns/Cr on short-TE MR spectroscopy. We correlated neurometabolic parameters with immunologic, clinical, data and combined antiretroviral therapy efficacy scores. RESULTS: There was a significant decrease in NAA/Cr (P < .05) in HIV-positive patients on and without combined antiretroviral therapy, compared with healthy controls in all locations. There were significant differences in Cho/Cr (P < .05) and mIns/Cr (P < .05) ratios between HIV+ patients on and without therapy, compared with healthy controls, but these differed in distribution. There were no significant differences in brain metabolite ratios between the 2 groups of chronically HIV-infected patients. The CNS penetration efficacy score showed weak positive correlations only with Cho/Cr ratios in some locations. CONCLUSIONS: The impact of combined antiretroviral therapy on the process of neuronal loss and dysfunction in chronic HIV infection appears to be suboptimal in successful peripheral suppression of viral replication. Spectroscopic imaging might be a useful tool for monitoring the effects of different combined antiretroviral therapy regimens on brain metabolite ratios.

Prediction of brain atrophy using three drug scores in neuroasymptomatic HIV-infected patients with controlled viremia

BACKGROUND Despite potent antiretroviral therapy, HIV still causes brain damage. Better penetration into the CNS and efficient elimination of monocyte/macrophages reservoirs are two main characteristics of an antiretroviral drug that could prevent brain damage. The aim of our study was to assess efficacy of three antiretroviral drug scores to predict brain atrophy in HIV-infected patients. METHODS A cross sectional study consisting of 56 HIV-infected patients with controlled viremia, who had no clinically evident neurocognitive impairment. All patients had MRI of the head. A typical T2 transversal slice was analyzed and ventricles-brain ratio (VBr) as an overall brain atrophy index was calculated. Three antiretroviral drug scores were used and correlated with VBr: 2008 and 2010 CNS penetration effectiveness scores (ΣCPE2008 and ΣCPE2010) and the recently established monocyte efficacy (ΣME) score. A p-value <0.05 was considered significant. RESULTS ΣCPE2010 was significantly associated with VBr in both univariate (r=-0.285, p=0.033) and multivariate (β=-0.299, p=0.016) regression models, while ΣCPE2008 was not (r=-0.141, p=0.300 and β=-0.156, p=0.214). ΣME was associated with VBr in multivariate model only (r=-0.297, p=0.111 and β=-0.406, p=0.029). Age and reported duration of HIV infection were also significant predictors of overall brain atrophy in multivariate regression models. CONCLUSIONS Although based on similar type of research, ΣCPE2010 is a superior drug score compared to ΣCPE2008. ΣME is an efficient drug score in determining brain damage. Both ΣCPE2010 and ΣME scores should be taken into account in preventive strategies of brain atrophy and neurocognitive impairment in HIV-infected patients.

Basal ganglia shrinkage without remarkable hippocampal atrophy in chronic aviremic HIV-positive patients

Conventional magnetic-resonance (MR) imaging is not sensitive enough in depicting subtle neurodegenerative changes that occur during chronic HIV infection with good peripheral viral suppression. The aim of this study was to compare brain volumes in HIV-positive subjects with age- and education-matched healthy controls with regard to influence of aging and immunologic parameters. An overall of 65 subjects (40 HIV-positive and 25 age-, gender-, and education-matched healthy subjects) underwent conventional MR imaging with three-dimensional sequence adequate for volumetric measurements. Volumes of specific brain regions were measured and compared between HIV-positive and healthy subjects using Student t test. Correlations between obtained brain volumes and immunologic parameters were determined using Pearson’s correlation test. Influence of age as a covariate was determined using ANCOVA test. Statistical value was set at p < 0.05. Volumes of nucleus accumbens (p = 0.003), putamen (p = 0.003), and thalamus (p = 0.046) were significantly decreased in HIV-positive subjects compared with healthy, while volumes of lateral ventricles were significantly increased (p = 0.043). However, influence of age on atrophy was greater than presence of HIV infection in all observed volumes. Positive correlation of nadir CD4+ count and nucleus accumbens volume was obtained, as well as of therapy with lateral ventricle volumes. Volumes of putamen correlated negatively with duration of therapy. HIV-associated atrophic changes are visible in nucleus accumbens, putamen, and thalamus in neurocognitively asymptomatic stage, while no changes can be observed in the hippocampus, affected by other types of dementias. Under therapy, the influence of physiological aging on HIV-associated atrophy is greater than the presence of HIV infection per se.

PITUITARNI APSCES NEUOBIČAJENOG KLINIČKOG TIJEKA

The aim is to present unusual clinical course and magnetic resonance imaging (MRI) features of pituitary abscess. A 59-year-old man presented with fever, polyuria, polydipsia and marked weight loss within the last two months. Basic endocrinology tests revealed the presence of anterior pituitary dysfunction, associated with central diabetes insipidus and increased levels of inflammatory markers. The presence of expansile sellar lesion, showing restricted diffusion signal pattern compatible with acute pituitary pyogenic abscess was found on MRI. Regression of pituitary abscess was obvious during the next few weeks of parenteral antibiotic treatment. Adequate substitution treatment with L thyroxine, hydrocortisone, testosterone and desmopressin was achieved. Seventeen months later, clinical deterioration associated with recurrent pituitary abscess was confirmed on MRI. Abscess regression was obvious again after conservative treatment. However, control MRI study performed three years after initial scanning revealed the presence of pituitary tumor, most consistent with macroadenoma. Surgical intervention was ordered. Histologic evaluation indicated the presence of fibrotic changes, associated with granulation tissue and rare cellular elements, compatible with chronic inflammation. To the best of our knowledge, there are no studies in the literature describing such a pattern of chronic evolution of pyogenic pituitary abscess with consequent chronic inflammatory changes with granulation tissue proliferation, mimicking macroadenoma.

Intradural extramedullary extraosseous Ewing sarcoma/PNET of foramen magnum.

Magnetic resonance imaging (MRI) of the cervical spine was ordered in a 19-year-old male athlete who presented with a left posterior and lateral neck pain. An intradural extramedullary mass showing intense homogeneous contrast enhancement was revealed in foramen magnum, encasing V4 segment of the left vertebral artery and displacing the ventral aspect of medulla oblongata and spinal cord (Fig. 1a, b), associated with perineural spread, affecting left C1 root (Fig. 1c). Partial reduction of the mass was performed. Histological evaluation revealed the presence of Ewing sarcoma (EWS)/peripheral primitive neuroectodermal tumor (pPNET). Complete regression of the tumor was noted after radiation treatment (Fig. 2a). However, cerebrospinal fluid dissemination was evident on follow-up MRI examinations several months later, involving spinal (Fig. 2b) and intracranial compartments (Fig. 2c). Intrathecal chemotherapy was not successful. Lethal outcome occurred 18 months after initial scanning. Foramen magnum tumors are typically benign. Meningiomas and neurinomas are the most frequent. Extraosseous form of EWS/pPNET affecting central nervous system is extremely rare, but should be considered in differential diagnosis of atypical aggressive tumors in young adults. Best to our knowledge, no prior reports of this neoplastic disease, affecting foramen magnum are available. Since most recent investigations indicate that both EWS and PNET share similar neural phenotype and have an identical chromosome translocation, they are considered as the same tumor, differing only in their degree of neural differentiation. The survival depends on the type of genetic rearrangements. The tumor occurs most commonly at the age of 10–30, peak incidence at the age of 15, with a male to female ratio of 1.4:1 [1]. Intracranial primary origin has also been reported [2].

Isolated Inflammatory Arthritis of the Atlantooccipital Joint Confused with Migraine

Magnetic resonance imaging (MRI) was performed in a 52-year-old woman with a several-year history of pharmacologically resistant, migraine-like, left hemicranial pain, lasting 48–72 h, accompanied with left eye “tunnel vision”. The presence of synovial effusion (Figure 1A and 1B) and associated dilated vein without erosions of the joint facets and cartilage (Figure 1C) were revealed on precontrast and postcontrast MRI, consistent with inflammatory arthritis …