Unusually severe muscular dystrophy upon in-frame deletion of the dystrophin rod domain and lack of compensation by membrane-localized utrophin.

Background: Utrophin, a dystrophin homolog, is consistently upregulated in muscles of patients with Duchenne muscular dystrophy (DMD) and is believed to partially compensate for the lack of dystrophin in dystrophic muscle. Even though several animal studies support the idea that utrophin can modulate DMD disease severity, human clinical data are scarce.

Methods: We describe a patient with the largest reported in-frame deletion in the DMD gene, including exons 10-60 and thus encompassing the entire rod domain.

Dysregulated Genes, MicroRNAs, Biological Pathways, and Gastrocnemius Muscle Fiber Types Associated With Progression of Peripheral Artery Disease: A Preliminary Analysis.

Background Peripheral artery disease (PAD) is associated with gastrocnemius muscle abnormalities. However, the biological pathways associated with gastrocnemius muscle dysfunction and their associations with progression of PAD are largely unknown. This study characterized differential gene and microRNA (miRNA) expression in gastrocnemius biopsies from people without PAD compared with those with PAD.

Mitochondrial DNA damage in calf skeletal muscle and walking performance in people with peripheral artery disease.

Background: Peripheral artery disease (PAD) is associated with mitochondrial dysfunction in calf skeletal muscle and a greater abundance of mitochondrial DNA (mtDNA) heteroplasmy. However, it is unknown whether calf skeletal muscle mtDNA of PAD participants harbors a greater abundance of mitochondrial DNA 4977-bp common deletion (mtDNA), strand breaks and oxidative damage (i.e.

Associations of Poly (ADP-Ribose) Polymerase1 abundance in calf skeletal muscle with walking performance in peripheral artery disease.

Objective: This study investigated associations of markers of oxidative stress and mitochondrial function in calf muscle biopsies with walking performance in people with and without lower extremity peripheral artery disease (PAD).

Methods: Participants with PAD (ankle-brachial index (ABI) <0.90) and without PAD (ABI: 0.

Correlations of Calf Muscle Macrophage Content With Muscle Properties and Walking Performance in Peripheral Artery Disease.

Background Peripheral artery disease (PAD) is a manifestation of atherosclerosis characterized by reduced blood flow to the lower extremities and mobility loss. Preliminary evidence suggests PAD damages skeletal muscle, resulting in muscle impairments that contribute to functional decline. We sought to determine whether PAD is associated with an altered macrophage profile in gastrocnemius muscles and whether muscle macrophage populations are associated with impaired muscle phenotype and walking performance in patients with PAD.

Associations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmy.

Background Patients with peripheral artery disease (PAD) undergo frequent episodes of ischemia-reperfusion in lower extremity muscles that may negatively affect mitochondrial health and are associated with impaired mobility. We hypothesized that skeletal muscle from PAD patients will show high mitochondrial DNA heteroplasmy, especially in regions more susceptible to oxidative damage, such as the displacement loop, and that the degree of heteroplasmy will be correlated with the severity of ischemia and mobility impairment. Methods and Results Mitochondrial mutations and deletions and their relative abundance were identified by targeted mitochondrial DNA sequencing in biopsy specimens of gastrocnemius muscle from 33 PAD (ankle brachial index <0.

Associations of Weight Change With Changes in Calf Muscle Characteristics and Functional Decline in Peripheral Artery Disease.

Background Among people with lower extremity peripheral artery disease, obesity is associated with faster functional decline than normal weight. The association of weight loss with functional decline in peripheral artery disease is unknown. Methods and Results Adults with an ankle-brachial index <0.

Open label study to assess the safety of VM202 in subjects with amyotrophic lateral sclerosis.

Objective: To assess safety and define efficacy measures of hepatocyte growth factor (HGF) DNA plasmid, VM202, administered by intramuscular injections in patients with amyotrophic lateral sclerosis (ALS).

Methods: Eighteen participants were treated with VM202 administered in divided doses by injections alternating between the upper and lower limbs on d 0, 7, 14, and 21. Subjects were followed for nine months to evaluate possible adverse events.

Walking performance is positively correlated to calf muscle fiber size in peripheral artery disease subjects, but fibers show aberrant mitophagy: an observational study.

Background: Patients with lower extremity peripheral artery disease (PAD) have decreased mobility, which is not fully explained by impaired blood supply to the lower limb. Additionally, reports are conflicted regarding fiber type distribution patterns in PAD, but agree that skeletal muscle mitochondrial respiration is impaired.

Methods: To test the hypothesis that reduced muscle fiber oxidative activity and type I distribution are negatively associated with walking performance in PAD, calf muscle biopsies from non-PAD (n = 7) and PAD participants (n = 26) were analyzed immunohistochemically for fiber type and size, oxidative activity, markers of autophagy, and capillary density.

Distal acquired demyelinating symmetric neuropathy after vaccination.

Neuropathy after vaccination is a rare event. Chronic immune-mediated polyneuropathy developing in the postvaccination period is distinctly unusual and not well described. Almost all such patients have been reported as having typical chronic inflammatory demyelinating polyneuropathy.

Gastrostomy tube placement by endoscopy versus radiologic methods in patients with ALS: a retrospective study of complications and outcome.

Gastrostomy tube placement for malnutrition and weight loss stabilization occurs in many patients with ALS. We sought to compare the outcome and complications of gastrostomy tube placement by endoscopic (PEG) and multiple radiologic (RIG) methods in ALS patients. A retrospective analysis was conducted on all ALS patients evaluated at Northwestern University who received gastrostomy tubes between January 2009 and March 2012.

SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis.

Background: The SQSTM1 gene encodes p62, a major pathologic protein involved in neurodegeneration.

Objective: To examine whether SQSTM1 mutations contribute to familial and sporadic amyotrophic lateral sclerosis (ALS).

Design: Case-control study.

Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia.

Amyotrophic lateral sclerosis (ALS) is a paralytic and usually fatal disorder caused by motor-neuron degeneration in the brain and spinal cord. Most cases of ALS are sporadic but about 5-10% are familial. Mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein (TARDBP, also known as TDP43) and fused in sarcoma (FUS, also known as translocated in liposarcoma (TLS)) account for approximately 30% of classic familial ALS.

Reversible demyelinating neuropathy associated with renal cell carcinoma.

Paraneoplastic neuropathy is a potential complication of renal cell carcinoma. The clinical and electrophysiologic features of such patients have not been well characterized. We describe a patient with a demyelinating neuropathy associated with papillary renal cell carcinoma that resolved following nephrectomy.

Promoting excellence in end-of-life care in ALS.

The type and quality of end-of-life care varies greatly in ALS; the time to initiate end-of-life care is not defined, and decision making is hampered by logistical and financial barriers. There has been no systematic review of these issues in ALS. The goals of this initiative are to: 1) improve end-of-life care for patients with ALS and families based on what limited evidence is available; 2) increase awareness, interest, and debate on the end-of-life care in ALS; and 3) identify areas needed for new prospective clinical research.

Compression of the brachial plexus during right lobe liver donation as a cause of brachial plexus injury: a case report.

We present a case of brachial plexus injury in a living-related liver donor, most likely caused by compression of the plexus between the 1st rib and clavicle, the result of rib retraction for surgical exposure.

Prolonged compound muscle action potential duration in critical illness myopathy: report of nine cases.

The objective of this study was to determine the diagnostic use of compound muscle action potential duration in patients with critical illness myopathy. Accurate diagnosis is important because the muscles recover once the offending agents are withdrawn. We retrospectively reviewed 9 cases seen at our institution between 1999 and 2003 in which critical illness myopathy was diagnosed on the basis of clinical and electrophysiological evaluations.

An outbreak of eosinophilic meningitis caused by Angiostrongylus cantonensis in travelers returning from the Caribbean.

Background: Outbreaks of eosinophilic meningitis caused by the roundworm Angiostrongylus cantonensis are rarely reported, even in regions of endemic infection such as Southeast Asia and the Pacific Basin. We report an outbreak of A. cantonensis meningitis among travelers returning from the Caribbean.