Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology characterized by spontaneous, involuntary movements and vocalizations called tics. Once thought to be rare, TS affects ...0.3–1% of the population. Tics can cause physical discomfort, emotional distress, social difficulties, and can interfere with education and desired activities. The pharmacologic treatment of TS is particularly challenging, as currently the genetics, neurophysiology, and neuropathology of this disorder are still largely unknown. However, clinical experience gained from treating TS has helped us better understand its pathogenesis and, as a result, derive treatment options. The strongest data exist for the antipsychotic agents, both typical and atypical, although their use is often limited in children and adolescents due to their side-effect profiles. There are agents in a variety of other pharmacologic categories that have evidence for the treatment of TS and whose side-effect profiles are more tolerable than the antipsychotics; these include clonidine, guanfacine, baclofen, topiramate, botulinum toxin A, tetrabenazine, and deutetrabenazine. A number of new agents are being developed and tested as potential treatments for TS. These include valbenazine, delta-9-tetrahydrocannabidiol, and ecopipam. Additionally, there are agents with insufficient data for efficacy, as well as agents that have been shown to be ineffective. Those without sufficient data for efficacy include clonazepam, ningdong granule, 5-ling granule, omega-3 fatty acids, and n-acetylcysteine. The agents that have been shown to be ineffective include pramipexole and metoclopramide. We will review all of the established pharmacologic treatments, and discuss those presently in development.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The cerebellum has a medial, cortico-nuclear zone consisting of the cerebellar vermis and the fastigial nucleus. Functionally, this zone is concerned with whole-body posture and locomotion. The ...vermis classically is thought to be included within the "spinocerebellum" and to receive somatic sensory input from ascending spinal pathways. In contrast, the lateral zone of the cerebellum is included in the "cerebro-cerebellum" because it is densely interconnected with the cerebral cortex. Here we report the surprising result that a portion of the vermis receives dense input from the cerebral cortex. We injected rabies virus into lobules VB–VIIIB of the vermis and used retrograde transneuronal transport of the virus to define disynaptic inputs to it. We found that large numbers of neurons in the primary motor cortex and in several motor areas on the medial wall of the hemisphere project to the vermis. Thus, our results challenge the classical view of the vermis and indicate that it no longer should be considered as entirely isolated from the cerebral cortex. Instead, lobules VB–VIIIB represent a site where the cortical motor areas can influence descending control systems involved in the regulation of whole-body posture and locomotion. We argue that the projection from the cerebral cortex to the vermis is part of the neural substrate for anticipatory postural adjustments and speculate that dysfunction of this system may underlie some forms of dystonia.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The most widely used white pigment of foods and medications is crystalline, anatase-phase TiO2 of 110 ± 70 nm particle diameter. Recent studies by other investigators have shown that depending on its ...ingested pigment amount the concentration of titanium in human blood ranges between 2 and 48 ppb and that Ti accumulates in the spleen and in the liver. Here we report titanium concentrations in the pancreas head of 30 human donors, measured by inductively coupled plasma quadrupole mass spectroscopy. Of the donors, 7 were free of pancreatic disease, 4 had pancreatitis, 10 had type 2 diabetes and 9 had type 2 diabetes with pancreatitis; 3 were underweight, 6 were normal weight, 5 were overweight, and 16 were obese. Ti accumulated in the pancreas, its accumulation increasing with obesity. The pancreatic Ti concentrations ranged from 0.75 to 3.78 ppm, averaging 1.8 ppm, much higher than the reported 40–100 ppb concentration in the spleen or the 30–100 ppb concentration reported in the liver. The corresponding number density of 110 nm diameter TiO2 particles averaged 3.6 × 109 per gram of wet tissue; their potentially biological macromolecule adsorbing surface area is ∼1 cm2 per gram wet tissue.
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IJS, KILJ, NUK, PNG, UL, UM
This work evaluates the use of potassium hydroxide (KOH) and potassium oxalate monohydrate (K2C2O4·H2O) for the formation of nitrogen- and oxygen-doped porous carbons. On the basis of molar ...equivalent amounts of potassium, we find that KOH activation generally produces porous carbons with larger fractions of mesopores (≥2 nm), while K2C2O4·H2O activation produces porous carbons with greater fractions of micropores (≤2 nm). Additionally, we investigate mechanisms of heteroatom loss during activation and find that nitrogen is exclusively sequestered in solid inorganic phases. Notably, differences in the surface properties of the resulting carbons are subtle. While surface nitrogen species are similar between both activation treatments, KOH activation produces materials with both a greater abundance and different types of surface oxygen species when compared to K2C2O4·H2O activation. Finally, we determine that the degree of carbon dioxide (CO2) adsorbed in the activated carbons at pressures up to 1 bar is primarily determined by the volume of small micropores (≤1 nm). Overall, this study seeks to provide a roadmap to tailor the surface and textural properties of heteroatom-doped porous carbons for gas storage, separations, and energy storage applications.
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IJS, KILJ, NUK, PNG, UL, UM
Hypomyelinating leukodystrophies comprise a subclass of genetic disorders with deficient myelination of the CNS white matter. Here we report four unrelated families with a hypomyelinating ...leukodystrophy phenotype harbouring variants in TMEM163 (NM_030923.5). The initial clinical presentation resembled Pelizaeus-Merzbacher disease with congenital nystagmus, hypotonia, delayed global development and neuroimaging findings suggestive of significant and diffuse hypomyelination. Genomic testing identified three distinct heterozygous missense variants in TMEM163 with two unrelated individuals sharing the same de novo variant. TMEM163 is highly expressed in the CNS particularly in newly myelinating oligodendrocytes and was recently revealed to function as a zinc efflux transporter. All the variants identified lie in highly conserved residues in the cytoplasmic domain of the protein, and functional in vitro analysis of the mutant protein demonstrated significant impairment in the ability to efflux zinc out of the cell. Expression of the mutant proteins in an oligodendroglial cell line resulted in substantially reduced mRNA expression of key myelin genes, reduced branching and increased cell death. Our findings indicate that variants in TMEM163 cause a hypomyelinating leukodystrophy and uncover a novel role for zinc homeostasis in oligodendrocyte development and myelin formation.
Pediatric Iatrogenic Movement Disorders Nagesh, Deepti; Goeden, Marcie; Coffman, Keith A.
Seminars in pediatric neurology,
April 2018, 2018-Apr, 2018-04-00, 20180401, Volume:
25
Journal Article
Peer reviewed
The acute development of a movement disorder is often a dramatic and frightening experience for patients and families, often requiring urgent or emergent evaluation by a neurologist. In the ...assessment of these patients, one relies on the history, physical and neurologic examination to determine the etiology of the condition. We aim to demonstrate that a thorough medication history is an incredibly critical part of this evaluation as iatrogenic movement disorders can arise from exposure not only to psychoactive medications, but from drugs prescribed for a variety of nonneurologic disorders. This comprehensive review is organized by movement disorder semiology so that the reader can more readily develop a differential diagnosis when evaluating a patient with a movement disorder.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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