Somatic mosaicism due to a reversion variant causing hemi-atrophy: a novel variant of dystrophinopathy.

We describe a case of hemi-atrophy in a young adult male, with a positive family history of three maternal uncles with Duchenne muscular dystrophy (DMD). The patient showed progressive weakness localized to the left side, an abnormal electromyography, and creatine kinase levels >3000 IU/l. Muscle biopsy showed both dystrophin-positive and -negative myofibers. An out-of-frame duplication variant in DMD, that is, c.(93+1_94-1)_(649+1_650-1)dup(p.?) resulting in duplication of exons 3-7 was inherited, but the muscle biopsy showed dystrophin mRNA with and without the duplication. Dystrophin quantification using mass spectrometry showed 25% normal dystrophin protein levels in the muscle biopsy from the stronger right side. Sex chromosome aneuploidy was ruled out. We conclude that the patient inherited the duplication variant, but early in development an inner cell mass underwent a somatic recombination event removing the duplication and restoring dystrophin expression. To our knowledge, this is the first report of a reversion leading to somatic mosaicism in DMD.

A male with progressive lower extremity weakness and monoclonal gammopathy.

EDUCATIONAL OBJECTIVES: To discuss a case of progressive lower extremity paresis and paresthesias in a patient found to have monoclonal gammopathy. KEY QUESTIONS: (1) What is the differential diagnosis of progressive lower extremity paresis and paresthesias? (2) How would one approach diagnostic testing for such a patient? (3) What is the differential diagnosis of neuropathy associated with gammopathy? and (4) What is the treatment for this patient?

Safety of a "drip and ship" intravenous thrombolysis protocol for patients with acute ischemic stroke.

BACKGROUND: The "drip and ship" approach for intravenous thrombolysis (IVT) is becoming the standard of care for patients with acute ischemic stroke (AIS) in communities without direct access to a stroke specialist. We aimed to demonstrate the safety of our "drip and ship" IVT protocol. METHODS: This was a retrospective study of patients with AIS treated with IVT between January 2003 and January 2011. Information on patients' baseline characteristics, neuroimaging, symptomatic intracerebral hemorrhage (sICH), and mortality was obtained from our stroke registry. A group of patients were treated with IVT by an emergency physician in phone consultation with a board-certified vascular neurologist (BCVN) at 1 of our 3 stroke network-affiliated hospitals (SNAHs). These patients were subsequently transferred to our Joint Commission-certified primary stroke center (CPSC) after completion of IVT ("drip and ship" protocol). The other patients were treated directly by a BCVN at the CPSC. RESULTS: We studied 201 patients treated with IVT. Of them, 14% received IVT at a SNAH ("drip and ship" protocol) and 86% were treated at the CPSC. There were no significant differences between the 2 groups with regard to age, National Institutes of Health Stoke Scale score, stroke symptom onset-to-needle time, sICH, or in-hospital mortality. CONCLUSIONS: Our "drip and ship" protocol for IVT is safe. The protocol was not associated with an excess of sICH or in-hospital mortality compared with patients who received IVT at the CPSC.