Paroxysmal Non-Kinesigenic Choreoathetosis Case Report and a Review of the Pathogenesis.

Paroxysmal dyskinesias are a rare group of episodic movement disorders characterized by any combination of dystonia, chorea, and athetosis. Patients usually present early in life with episodes of variable frequency involving the limbs or facial muscles that can be disabling. In this article, we present a case of paroxysmal non-kinesigenic dyskinesia that was responsive to the sodium-channel blocker carbamazepine. Recent data has revealed the role of voltage-gated sodium channels in the pathophysiology of the disease; hence, these disorders are referred to as channelopathies. Further advancements in genetic analysis have elucidated targets corresponding to these disorders, indicating a possible role for gene sequencing in helping to differentiate the subtypes of paroxysmal dyskinesias. This case report sheds light on the pathophysiology of the various channelopathies, especially the findings of cerebellar spreading depolarization and its implication in paroxysmal kinesigenic and non-kinesigenic dyskinesias.

Use of an Intracranial Drain as a Conduit for Treatment of an Intracranial Streptococcus intermedius Abscess.

Brain abscesses are difficult to manage clinically and often result in a poor outcome. Although surgical and medical therapeutics have progressed, there are still challenges that make treating intracranial abscesses problematic. One of these treatment barriers is the poor penetration of intravenous antibiotics to the infection source through the blood-brain barrier. In this case report, we will discuss the use of a surgical drain as a conduit for direct antibiotic administration for a rare, recurrent Streptococcus intermedius infection. This technique allows us to bypass the blood-brain barrier while also reducing the systemic effects of antibiotics. When used in conjunction with craniotomy and resection, direct antibiotic administration via a surgical drain proved to be effective at treating our patient's abscess and preventing recurrence.

Child Abuse: The Consequence of an Undiagnosed Giant Olfactory Groove Meningioma?

Olfactory groove meningiomas are slow-growing tumors that manifest with headaches, changes in vision, and personality changes. The anatomic location of these tumors makes psychiatric disturbances more common early in the stage of tumors than focal neurological deficits. The case study here describes a unique instance of an undiagnosed giant olfactory groove meningioma in a young mother who was charged with a felony of aggravated child abuse for the death of her toddler daughter. The patient underwent gross tumor resection and radiation therapy, which halted the visual decline, resolved the frontal headaches, and the patient showed improved mood. In this patient, the insidious onset of personality changes without obvious focal neurologic deficits until late as well as a history of depression likely contributed to the delayed diagnosis. Failure to notice these initial behavioral manifestations in these patients allows for further psychiatric and cognitive decline, which can result in devastating social consequences.

Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts.

Patient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neuroblastoma PDXs in vitro. Cells were treated with two small molecule inhibitors of FAK, PF-573,228 (PF) and 1,2,4,5-benzentetraamine tetrahydrochloride (Y15). Following FAK inhibition, cell survival and proliferation decreased significantly and cell cycle arrest was seen in both cell lines. Migration and invasion assays were used to determine the effect of FAK inhibition on cell motility, which decreased significantly in both cell lines in the presence of either inhibitor. Finally, tumor cell stemness following FAK inhibition was evaluated with extreme limiting dilution assays as well as with immunoblotting and quantitative real-time PCR for the expression of stem cell markers. FAK inhibition decreased formation of tumorspheres and resulted in a corresponding decrease in established stem cell markers. FAK inhibition decreased many characteristics of the malignant phenotype, including cancer stem cell like features in neuroblastoma PDXs, making FAK a candidate for further investigation as a potential target for neuroblastoma therapy.

Striatal Interneurons in Transgenic Nonhuman Primate Model of Huntington's Disease.

Huntington's disease is an autosomal dominant neurodegenerative disorder associated with progressive motor and cognitive impairments, and the expansion of a cysteine-adenine-guanine trinucleotide (polyglutamine) repeats in exon one of the human huntingtin gene. The pathology of the disease is characterized by a profound degeneration of striatal GABAergic projection neurons with relative sparing of interneurons accompanied with astrogliosis. Here, we describe the striatal pathology in two genotypically different transgenic HD monkeys that exhibit degrees of disease progression that resembled those seen in juvenile- (rHD1) and adult-onset (rHD7) HD. The caudate nucleus and putamen underwent severe neuronal loss in both animals, while the striatal volume was reduced only in rHD1, the most severely affected monkey. The number of GABAergic (calretinin- and parvalbumin-positive) and cholinergic interneurons was also reduced in most striatal regions of these two monkeys, but to variable degrees. Overall, the density of interneurons was increased in rHD1, but not in rHD7, suggesting a relative sparing of interneurons over projection neurons in the striatum of the most affected HD monkey. The neuropil of both the caudate nucleus and putamen was invaded with reactive astrocytes in rHD1, while astrogliosis was much less severe in rHD7 and absent from control. Combined with behavioral data collected from these monkeys, our findings further demonstrate that transgenic HD monkeys share similar disease patterns with HD patients, making them a highly reliable preclinical HD animal model.