Primary familial brain calcification in the 'IBGC2' kindred: All linkage roads lead to SLC20A2.

BACKGROUND: Linkage analyses of families with primary familial brain calcification (formerly idiopathic basal ganglia calcification [IBGC]) identified 3 candidate loci (IBGC1-3). Recently, SLC20A2 mutations were found in the IBGC1 and IBGC3 families, merging these 2 loci. We here elucidate the genetic cause of primary familial brain calcification in the 'IBGC2' kindred. METHODS: We sequenced known primary familial brain calcification genes and quantified SLC20A2 and PDGFB. Moreover, CT scans of affected and unaffected family members were evaluated by 2 blinded neuroradiologists for distribution of brain calcification. RESULTS: A heterozygous multiexonic SLC20A2 deletion was detected in several affected family members. A reevaluation of neuroimaging data revealed a subset of mutation-negative individuals with only mild and/or unilateral calcification. CONCLUSIONS: The identified SLC20A2 mutation resolves the genetic cause of primary familial brain calcification in the 'IBGC2' kindred, collapsing 'IBGC2' into IBGC1. We suggest an algorithm for predicting the chances of finding genetic mutations that has to be validated in further studies. Our study enhances criteria for the evaluation of neuroimaging data, contributing further to the much needed harmonization of diagnostic and research data collection in primary familial brain calcification. © 2016 International Parkinson and Movement Disorder Society.

Intrathecal liposomal cytarabine in combination with temozolomide in low-grade oligoastrocytoma with leptomeningeal dissemination.

Leptomeningeal dissemination of low-grade gliomas is an uncommon event. A 43-year old male presented with dizziness, gait ataxia, and diplopia. A nonenhancing lesion in the right cerebellar peduncle was identified, subtotally resected, and diagnosed as a grade II astrocytoma. After one year a nodular spread in the brain and leptomeninges was diagnosed, so the patient started chemotherapy with temozolomide and liposomal cytarabine. Complete remission was achieved after 12 months of treatment and the patient is still free from the disease after a follow-up of 24 months. We suggest that this combination may be a valuable treatment option.

Intravascular lymphomatosis and intracerebral haemorrhage.

Intravascular lymphomatosis (IVL) is a rare, malignant B- or T-cell lymphoma with remarkable affinity for the endothelial cells of small vessels, particularly within the skin and central nervous system. It is a disease that mimics several neurological disorders, particularly those of cerebrovascular ischemic origin. The prognosis is generally poor, with a rapidly fatal outcome. As a result the diagnosis is often made at post-mortem. We report a rare case of a 73-year-old patient with IVL complicated by intracerebral haemorrhage. In literature two cases of systemic IVL complicated by intracerebral haemorrhage have been reported, but they presented initially with a disseminated intravascular coagulation (DIC). This is the first case of brain IVL complicated by intracerebral haemorrhage not associated to DIC. Increasing awareness of this disease as a differential diagnosis to a common clinical presentation may lead to more opportunities to evaluate new diagnostic and treatment approaches.

Exclusion of linkage to chromosome 14q in a large South Tyrolean family with Idiopathic Basal Ganglia Calcification (IBGC).

Familial Idiopathic Basal Ganglia Calcification (FIBGC) is a neurodegenerative syndrome that usually follows an autosomal dominant pattern of inheritance. Linkage to only one locus on chromosome 14q (IBCG1) has been described so far. We identified and characterized a large multigenerational Italian family from a population isolate with 14 FIBGC affected members. Linkage analysis excluded the IBCG1 locus, thus demonstrating further locus heterogeneity for this disease.

Aortic and Mitral Valve Involvement in Maroteaux-Lamy Syndrome VI: Surgical Implications in the Enzyme Replacement Therapy Era.

Open-heart operations in patients with mucopolysaccharidoses are exceedingly rare and pose distinct clinical challenges. Few reports exist of valve replacement in type VI mucopolysaccharidosis, mostly entailing combined mitral and aortic valve replacement. Here reported is the case of a young woman with mitral and aortic valve disease, in whom the surgical procedure was confined to the aortic valve. The rationale behind this strategy, particularly in light of the benefits offered by specific enzyme replacement therapy of type VI mucopolysaccharidosis, is discussed.

Motor cortex excitability in transient global amnesia.

OBJECTIVE: To investigate the physiology of motor cortical areas in patients with transient global amnesia (TGA). MATERIALS AND METHODS: We performed transcranial magnetic stimulation (TMS) and single photon emission computed tomography (SPECT) in 13 patients during and after the acute phase of a typical episode of TGA. Measures of cortical excitability included motor threshold (MT) to magnetic stimulation, cortical silent period (SP) duration and intracortical inhibition (ICI) using a paired-pulse TMS technique. RESULTS: We found thalamic hypoperfusion and an ipsilateral significantly decreased ICI during the acute phase of TGA. CONCLUSIONS: Reduced activity in inhibitory circuits may explain why PET studies of patients with TGA showed neocortical hypometabolism. Our findings are consistent with the hypothesis that frontal cortex dysfunction probably due to damage affecting the thalamocortical circuits may play an important role in the pathogenesis of the syndrome.

Difficulties in diagnosing slowly progressive mucopolysaccharidosis VI: A case series.

An Erratum for this article can be found here: http://iospress.metapress.com/content/e16437020701m0u5/?p=df8dd6709cf44367a0c0e5d917aaeddf&pi=11We describe the cases of two adult sisters recently diagnosed with the attenuated form of mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome). MPS VI is a rare, clinically heterogeneous lysosomal storage disorder that is characterized by a deficiency in the glycosaminoglycan-degrading enzyme arylsulfatase B. Both cases had been misdiagnosed for over 30 years despite the presence of several characteristics of the disease, including short stature (mild), coarse facial features, skeletal dysmorphisms, carpal tunnel syndrome, heart valve disease, and spinal cord compression, which together are suggestive of a lysosomal storage disease. Awareness about the clinical features of MPS VI should be communicated amongst treating neurologists, rheumatologists and other specialists who are involved in the healthcare decisions of these patients with presenting symptoms, so they can refer them to specialized centers for proper diagnosis and treatment.

2q37 as a susceptibility locus for idiopathic basal ganglia calcification (IBGC) in a large South Tyrolean family.

Familial idiopathic basal ganglia calcification (FIBGC) is an inherited neurodegenerative disorder characterized by the accumulation of calcium deposits in different brain regions, particularly in the basal ganglia. FIBGC usually follows an autosomal dominant pattern of inheritance. Despite the mapping to chromosome 14q of a susceptibility locus for IBGC (IBCG1) in one family, this locus has been excluded in several others, demonstrating genetic heterogeneity in this disorder. The etiology of this disorder thus remains largely unknown. Using a large extended multigenerational Italian family from South Tyrol with 17 affected in a total of 56 members, we performed a genome-wide linkage analysis in which we were able to exclude linkage to the IBCG1 locus on chromosome 14q and obtain evidence of a novel locus on chromosome 2q37. Electronic supplementary material. The online version of this article (doi:10.1007/s12031-009-9287-3) contains supplementary material, which is available to authorized users.