Polymicrogyria with dysmorphic basal ganglia? Think tubulin!

Dominant mutations in TUBB2B have been reported in patients with polymicrogyria. We further explore the phenotype associated with mutations in TUBB2B. Twenty patients with polymicrogyria (five unilateral) were tested for mutations in TUBB2B by Sanger sequencing. We identified two novel de novo mutations, c.743C>T (p.Ala248Val) and c.1139G>T (p.Arg380Leu) in exon 4 of TUBB2B in three unrelated families. Brain magnetic resonance images showed polymicrogyria involving predominantly the perisylvian regions. In addition, there was a dysmorphic appearance of the basal ganglia, thin corpus callosum, enlargement of the ventricles, thinning of the white matter and hypoplasia of pons and cerebellar vermis. This combination of associated features was absent in all 17 patients with polymicrogyria in whom no mutation was identified. This report underlines that the association of polymicrogyria with thin or absent corpus callosum, dysmorphic basal ganglia, brainstem and vermis hypoplasia is highly likely to result from mutations in TUBB2B and provides further insight in how mutations in TUBB2B affect protein function.

Microwave-assisted synthesis and characterization of novel chitosan-based biomaterials for pelvic organ prolapse treatment.

Pelvic organ disorders affect up to one in four women in the United States. The prevalence of pelvic organ prolapse (POP) is increasing with each year, particularly in the setting of prolonged life expectancy and an aging population. Current treatment approaches, including polypropylene monofilaments are associated with numerous painful and worrisome side-effects. Therefore, scientists are looking for new solutions. A promising alternative to the current treatment is tissue engineering, which can be utilized to re-create support to the vagina and pelvic organs. Tissue engineering requires the use of three-dimensional scaffolds, derived from biocompatible materials. Chitosan is a natural polymer, obtained from shellfish exoskeletons. It is known for its biodegradability, lack of cytotoxicity and non-pyrogenicity. Due to the presence of free hydroxyl and amino groups, it may undergo various modifications. In this paper, we describe a new type of chitosan-based biomaterials, which can be used as a new alternative scaffold that may provide support to prolapse organs. The chitosan scaffold was obtained under microwave radiation using multifunctional amino and organic acids. We discuss the scaffold's characteristics, with an emphasis on its chemical structure and morphology. Fourier transform infrared spectroscopy (FT-IR) analysis confirmed cross-linking processes with preservation of free amino groups. Moreover, mechanical durability, the stability and swelling ability of the scaffolds in a simulated body fluid were investigated. All of the prepared scaffolds demonstrated very good antioxidant activity and biodegradability. Importantly, the biocompatibility of chitosan scaffolds was examined on human vaginal VK2/E6E7 cell line. No evidence of toxicity was documented, and the cells maintained their presence on the studied materials. These results allude to the lack of toxicity of the scaffolds, and indicate that chitosan-based scaffold should be further investigated in in vivo studies as they may be a promising alternative treatment to pelvic organ prolapse.

A clinical diagnostic algorithm for early onset cerebellar ataxia.

Early onset cerebellar Ataxia (EOAc) comprises a large group of rare heterogeneous disorders. Determination of the underlying etiology can be difficult given the broad differential diagnosis and the complexity of the genotype-phenotype relationships. This may change the diagnostic work-up into a time-consuming, costly and not always rewarding task. In this overview, the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society (CACG-EPNS) presents a diagnostic algorithm for EOAc patients. In seven consecutive steps, the algorithm leads the clinician through the diagnostic process, including EOA identification, application of the Inventory of Non-Ataxic Signs (INAS), consideration of the family history, neuro-imaging, laboratory investigations, genetic testing by array CGH and Next Generation Sequencing (NGS). In children with EOAc, this algorithm is intended to contribute to the diagnostic process and to allow uniform data entry in EOAc databases.

Familial periodic paralysis with hypokalaemia. Study of a muscle biopsy in the myopathic stage of the disorder.

A 51 year-old male patient was affected by a dominantly inherited periodic paralysis. With large potassium supplements and ageing, the number and severity of attacks became considerably reduced. Increasing weakness and atrophy of the lower extremities were documented by clinical examination and by computer-assisted tomography of the muscles. A biopsy was taken in the vastus lateralis muscle without any attempt to induce a hypokalaemic paralytic attack. Light microscopy showed multiple intra- and extracellular vacuoles, rimmed vacuoles, myonecrosis, fatty degeneration and endomysial fibrosis. The endomysial nerve bundles were normal. Both fiber types were vacuolated. Quantitative studies revealed abnormal variability coefficients and increased atrophy factors for all types. Electron microscopy showed dilatations of the tubular system and of the sarcoplasmic reticulum communicating with large vacuoles limited by a single membrane. Other vacuoles were covered by a basement membrane and could contain collagen fibers or capillaries. Accumulation of myeloid bodies and of 10-13 nm filaments were also noted in the sarcoplasm. Cytoplasmic bodies were present. No tubular aggregates could be found. The nerve bundles were normal. These findings were in part similar to the ones reported by Gérard et al. (1978) in the son's biopsy during an induced paralytic attack. Significant findings in our case are the sequence of events leading to muscle fibre destruction, still detectable at an advanced stage of the disease. Myopathic changes represent a delayed but severe complication of the disorder.

MRI of acute disseminated encephalomyelitis after coxsackie B infection.

Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating condition of the central nervous system, usually developing after a viral infection or vaccination. We report a case of ADEM predominantly affecting the spinal cord in an 8-year old boy evaluated by MRI. The radiographic picture consisted of multiple focal lesions of the spinal cord, a left posterior thalamic lesion and a subcortical right posterior parietal lesion. These lesions regressed several weeks after corticosteroid treatment. The clinical presentation, the laboratory results and the radiological findings suggest the diagnosis of ADEM secondary to viral infection by Coxsackie B.

Reversible striatal hypermetabolism in a case of Sydenham's chorea.

We studied a 10-year-old girl with Sydenham's chorea (SC) using positron emission tomography (PET) with fluorodeoxyglucose (FDG). Choreic movements involved the head and the left side of her body. PET showed increased glucose metabolism in the right caudate nucleus and putamen. Three months after complete recovery, striatal glucose metabolism had returned to normal in the caudate nucleus. In the right putamen, glucose metabolism had decreased compared to that in the first study but remained elevated compared to that of normal young adults. We propose that the transient striatal hypermetabolism may have been due to increased afferent inputs to the striatum as a consequence of striatal or subthalamic nucleus dysfunction.