Sparing of extraocular muscle in aging and muscular dystrophies: a myogenic precursor cell hypothesis.

The extraocular muscles (EOM) are spared from pathology in aging and many forms of muscular dystrophy. Despite many studies, this sparing remains an enigma. The EOM have a distinct embryonic lineage compared to somite-derived muscles, and we have shown that they continuously remodel throughout life, maintaining a population of activated satellite cells even in aging. These data suggested the hypothesis that there is a population of myogenic precursor cells (mpcs) in EOM that is different from those in limb, with either elevated numbers of stem cells and/or mpcs with superior proliferative capacity compared to mpcs in limb. Using flow cytometry, EOM and limb muscle mononuclear cells were compared, and a number of differences were seen. Using two different cell isolation methods, EOM have significantly more mpcs per mg muscle than limb skeletal muscle. One specific subpopulation significantly increased in EOM compared to limb was positive for CD34 and negative for Sca-1, M-cadherin, CD31, and CD45. We named these the EOMCD34 cells. Similar percentages of EOMCD34 cells were present in both newborn EOM and limb muscle. They were retained in aged EOM, whereas the population decreased significantly in adult limb muscle and were extremely scarce in aged limb muscle. Most importantly, the percentage of EOMCD34 cells was elevated in the EOM from both the mdx and the mdx/utrophin(-/-) (DKO) mouse models of DMD and extremely scarce in the limb muscles of these mice. In vitro, the EOMCD34 cells had myogenic potential, forming myotubes in differentiation media. After determining a media better able to induce proliferation in these cells, a fusion index was calculated. The cells isolated from EOM had a 40% higher fusion index compared to the same cells isolated from limb muscle. The EOMCD34 cells were resistant to both oxidative stress and mechanical injury. These data support our hypothesis that the EOM may be spared in aging and in muscular dystrophies due to a subpopulation of mpcs, the EOMCD34 cells, that are retained in significantly higher percentages in normal, mdx and DKO mice EOM, appear to be resistant to elevated levels of oxidative stress and toxins, and actively proliferate throughout life. Current studies are focused on further defining the EOMCD34 cell subtype molecularly, with the hopes that this may shed light on a cell type with potential therapeutic use in patients with sarcopenia, cachexia, or muscular dystrophy.

Regional cerebral hyperperfusion associated with postictal paresis.

The pathophysiology of postictal paresis and other symptoms of Todd's phenomenon are not fully understood. Various hypotheses about its mechanism include exhaustive neuronal firing, desensitization, and active suppression. This case series demonstrates CT perfusion findings of two patients with postictal paresis that show hyperperfusion, increased cerebral blood flow, increased cerebral blood volume, and decreased mean transit time in the intracranial distribution corresponding with neuronal symptoms. These findings may suggest an active process requiring adequate perfusion during Todd's phenomenon.

Rates and risks of gastrostomy tubes in infants with cleft palate.

OBJECTIVES: To review data on a cohort of infants with cleft palate to (1) determine rates of gastrostomy (G)-tube placement, (2) identify contributing comorbidities, and (3) use relative risk analyses to improve management of cleft palate in infants with feeding difficulty. DESIGN: Retrospective medical record review. SETTING: Tertiary care children's hospital. PATIENTS: Infants with cleft palate born between January 1, 2000, and December 31, 2008, without G-tubes prior to referral were included. Comorbidities were analyzed, including syndromes and chromosomopathies (syn/chrom) and cardiac, respiratory, neurologic, and gastrointestinal diagnoses. These comorbidities were analyzed independently. MAIN OUTCOME MEASURE: Gastrostomy-tube placement. RESULTS: Of 214 infants with cleft palate, 34 required G-tubes. Of these, 19 had syn/chrom. Independent of these diagnoses, 17 infants had 1 system comorbidity and 12 had multisystem comorbidities. Of the 180 patients without G-tubes, 20 had syn/chrom. Independent of these diagnoses, 10 infants had 1 system comorbidity and 2 had multisystem comorbidities. Rates of G-tube placement ranged from 3% in infants without any comorbidity to 94% in infants with respiratory comorbidity. Relative risks of G-tube placement with syn/chrom, 1 system comorbidity, and multisystem comorbidities were 5.68 (95% confidence interval, 3.18-10.16), 21.79 (8.76-54.17), and 29.66 (12.18-72.21), respectively. CONCLUSIONS: Diagnosis of syn/chrom or major comorbidity significantly increases risk of G-tube placement. Regardless of syn/chrom association, problems affecting the heart, respiratory system, central nervous system, and lower esophageal sphincter are the most significant risk factors, implying that particular comorbidities are more influential than a simple diagnosis of syn/chrom. These data should help identify children at greatest risk for G-tubes and those expected to overcome feeding difficulties, leading to more persistent use of nonsurgical therapy before resorting to G-tubes.