Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1.

Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. To identify the causative gene(s), exome sequencing was performed in a family with two affected siblings. Assuming autosomal recessive inheritance, two novel sequence variants were identified in both siblings in CYP26C1-a duplication of seven base pairs, which was maternally inherited, c.844_851dupCCATGCA, predicting p.Glu284fsX128 and a missense mutation, c.1433G>A, predicting p.Arg478His, that was paternally inherited. The duplication predicted a frameshift mutation that led to a premature stop codon and premature chain termination, whereas the missense mutation was not functional based on its in vitro expression in mammalian cells. The FFDD skin lesions arise along the sites of fusion of the maxillary and mandibular prominences early in facial development, and Cyp26c1 was expressed exactly along the fusion line for these facial prominences in the first branchial arch in mice. Sequencing of four additional, unrelated Type IV FFDD patients and eight Type II or III TWIST2-negative FFDD patients revealed that three of the Type IV patients were homozygous for the duplication, whereas none of the Type II or III patients had CYP26C1 mutations. The seven base pairs duplication was present in 0.3% of healthy controls and 0.3% of patients with other birth defects. These findings suggest that the phenotypic manifestations of FFDD Type IV can be non-penetrant or underascertained. Thus, FFDD Type IV results from the loss of function mutations in CYP26C1.

Quantitative detection of cirrhosis: towards the development of computer-assisted detection method.

There are distinct morphologic features of cirrhosis on CT examinations; however, such impressions may be subtle or subjective. The purpose of this study is to build a computer-aided diagnosis (CAD) method to help radiologists with this diagnosis. One hundred sixty-seven abdominal CT examinations were randomly divided into training (n = 88) and validation (n = 79) sets. Livers were analyzed for morphological markers of cirrhosis and logistic regression models were created. Using the area under curve (AUC) for model performance, the best model had 0.89 for the training set and 0.85 for the validation set. For radiology reports, sensitivity of reporting cirrhosis was 0.45 and specificity 0.99. Using the predictive model adjunctively, radiologists' sensitivity increased to 0.63 and specificity slightly decreased to 0.97. This study demonstrates that quantifying morphological features in livers may be utilized for diagnosing cirrhosis and for developing a CAD method for it.

Bilateral Painful Hand Seizures: An Atypical Somatotopic Syndrome.

Painful Hand Seizures are a rarely reported form of secondary sensory seizures (SSS) characterized by painful, bilateral sensorimotor hand involvement and preserved consciousness. We report our case to aid neurologists in recognizing SSS as an atypical presentation of seizures.

Location-atypical lesions in non-ketotic hyperglycemic epilepsy: expanding the clinico-radiographic phenotype

Non-ketotic hyperglycemia (NKH) is associated with a spectrum of symptoms and radiographic findings due to poorly-controlled diabetes mellitus. These lesions, which predominantly affect the parieto-occipital cortex, are commonly missed by neurologists and neuroradiologists due to their subtle hypointense appearance on T2-based imaging. We report four atypical cases of this syndrome to highlight its subtle, protean presentation in order to aid timely diagnosis. Based on our institutional case series, we describe four cases of NKH with atypical presentation and lesion burden affecting the anterior cortex. We review the clinical presentations, laboratory abnormalities, neuroimaging, and corresponding electroencephalography. Four patients with atypical NKH were characterized in our series. Presenting symptoms ranged from rhythmic hand-tapping to generalized tonic-clonic status epilepticus. Laboratory values were notable for marked hyperglycemia (range: 447 - 627 mg/dL), mild pseudo-hyponatremia (range: 127 - 136 mmol/L), and elevated hemoglobin A1C levels (range: 10.9 - 16.1%). All patients were found to have the classically described pattern of T2-based hypointensity; three with atypical distributions involving the "anterior" cortex. These lesions corresponded to the electrographic nidus of seizure burden. During follow-up, both seizures and T2-based hypointensity resolved within weeks of serum glucose normalization. Our series of four NKH patients with atypical findings of T2-based signal abnormalities expands the clinico-radiographic phenotype revealing a more protean distribution than previously described. Knowledge of these atypical imaging features will aid both the neurologist and radiologist in timely diagnosis and care of these patients.

Comparison of single-channel EEG, actigraphy, and sleep diary in cognitively normal and mildly impaired older adults.

STUDY OBJECTIVES: Multiple methods for monitoring sleep-wake activity have identified sleep disturbances as risk factors for Alzheimer disease (AD). In order to identify the level of agreement between different methods, we compared sleep parameters derived from single-channel EEG (scEEG), actigraphy, and sleep diaries in cognitively normal and mildly impaired older adults. METHODS: Two hundred ninety-three participants were monitored at home for up to six nights with scEEG, actigraphy, and sleep diaries. Total sleep time (TST), sleep efficiency (SE), sleep onset latency (SOL), and wake after sleep onset (WASO) were calculated using each of these methods. In 109 of the 293 participants, the ratio of cerebrospinal fluid concentrations of phosphorylated tau (p-tau) and amyloid-ß-42 (Aß42) was used as a biomarker for AD pathology. RESULTS: Agreement was highest for TST across instruments, especially in cognitively normal older adults. Overall, scEEG and actigraphy appeared to have greater agreement for multiple sleep parameters than for scEEG and diary or actigraphy and diary. Levels of agreement between scEEG and actigraphy overall decreased in mildly impaired participants and those with biomarker evidence of AD pathology, especially for measurements of TST. CONCLUSIONS: Caution should be exercised when comparing scEEG and actigraphy in individuals with mild cognitive impairment or with AD pathology. Sleep diaries may capture different aspects of sleep compared to scEEG and actigraphy. Additional studies comparing different methods of measuring sleep-wake activity in older adults are necessary to allow for comparison between studies using different methods.

Rapid Recovery With Plasma Exchange in Acute Motor Axonal Neuropathy With Reversible Conduction Failure.

Characterization of Guillain-Barré syndrome (GBS) subtypes has become increasingly complicated with the recognition of paranodal dysfunction and reversible conduction failure (RCF) in acute motor axonal neuropathy. We describe 2 cases of seronegative acute motor axonal neuropathy with RCF with a rapid onset of severe quadriplegia. Treatment with plasma exchange was associated with rapid clinical and electrophysiological response on serial examinations. Increased recognition of RCF may lead to improved characterization of GBS subtypes and may play a role in determining future treatment options in GBS.

Hepatic cytochrome p450-2A and phosphoribosylpyrophosphate synthetase-associated protein mRNA are induced in gerbils after consumption of isoflavone-containing protein.

Soy intake reduces cholesterol levels, but neither the exact component in soy causing this reduction nor the mechanism by which cholesterol is reduced is known with certainty. In this study, a genetic screen was performed to identify hepatic mRNA in gerbils regulated by soy or soy isoflavones. Gerbils were fed casein, an alcohol-washed soy-based diet (containing low levels of isoflavones), and the soy-based diet supplemented with an isoflavone-containing soy extract. After feeding for 28 d, gerbils were killed, hepatic RNA was isolated, and genes that were differentially expressed in any of the three dietary conditions were identified. Fifteen different mRNA were originally selected, including two mRNA that were studied further and shown to be highly regulated. Messenger RNA levels for both cytochrome P450-2A and phosphoribosylpyrophosphate synthetase-associated protein were up-regulated in a dose-dependent manner when soy replaced casein in the diet at 0, 33, 67 and 100% of original casein levels. A subsequent experiment used purified amino acid mixtures resembling the percentage amino acid composition of soy and casein to ensure that isoflavone-free protein sources could be tested. Using these mixtures, a 2 x 2 x 2 design tested: natural vs. synthetic protein sources, casein- vs. soy-based diets, and isoflavone extract-supplemented or supplement-free diets. This design demonstrated that these two mRNA were again significantly up-regulated more than twofold (P < 0.05) in gerbils fed all diets containing isoflavones. Induction of these two mRNA by soy may be due to the aryl hydrocarbon receptor element in the promoter region of both genes.