Investigating Late-Onset Pompe Prevalence in Neuromuscular Medicine Academic Practices: The IPaNeMA Study.

Background and Objectives: We investigated the prevalence of late-onset Pompe disease (LOPD) in patients presenting to 13 academic, tertiary neuromuscular practices in the United States and Canada. Methods: All successive patients presenting with proximal muscle weakness or isolated hyperCKemia and/or neck muscle weakness to these 13 centers were invited to participate in the study. Whole blood was tested for acid alpha-glucosidase (GAA) assay through the fluorometric method, and all cases with enzyme levels of ≤10 pmoL/punch/h were reflexed to molecular testing for mutations in the GAA gene. Clinical and demographic information was abstracted from their clinical visit and, along with study data, entered into a purpose-built REDCap database, and analyzed at the University of California, Irvine. Results: GAA enzyme assay results were available on 906 of the 921 participants who consented for the study. LOPD was confirmed in 9 participants (1% prevalence). Another 9 (1%) were determined to have pseudodeficiency of GAA, whereas 19 (1.9%) were found to be heterozygous for a pathogenic GAA mutation (carriers). Of the definite LOPD participants, 8 (89%) were Caucasian and were heterozygous for the common leaky (IVS1) splice site mutation in the GAA gene (c -32-13T>G), with a second mutation that was previously confirmed to be pathogenic. Discussion: The prevalence of LOPD in undiagnosed patients meeting the criteria of proximal muscle weakness, high creatine kinase, and/or neck weakness in academic, tertiary neuromuscular practices in the United States and Canada is estimated to be 1%, with an equal prevalence rate of pseudodeficiency alleles. Trial Registration Information: Clinical trial registration number: NCT02838368.

Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis.

OBJECTIVE: To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. METHODS: Two multicenter randomized, double-blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase. RESULTS: The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p = 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form-36 was also better in HOP participants receiving DCP (treatment effect = 7.29 points, 95% confidence interval 2.26 to 12.32, p = 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p = 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined). CONCLUSIONS: DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis. CLASSIFICATION OF EVIDENCE: These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP.

Cervical Myelopathy Caused by Injections into the Neck.

Three cases of longitudinally extensive cervical myelopathies temporally associated with neck injections are presented. The spinal cord injury was similar radiographically, despite a number of different needle approaches and substances injected. In recent years, there have been reports of an acute cervical myelopathy immediately following an injection procedure in the neck. Various explanations have been offered for this unfortunate complication, including (1) direct injection into the cord leading to traumatic injury, (2) injection of particulate matter into the arterial supply of the cord causing microvascular embolism and spinal cord infarction, and (3) intraneural injection of the chemical with centripetal spread of the injectant from the nerve trunk to the substance of the cord. The merits of each of these 3 mechanisms in explaining these cases are discussed. Albeit rare, acute cervical myelopathy should be considered a potential complication from any deep injection of chemicals into the neck.

Quantitative ultrasound of denervated hand muscles.

INTRODUCTION: Presentations to the neuromuscular clinic commonly involve hand muscle denervation, but few studies have evaluated hand muscle ultrasound. METHODS: Ultrasound studies of abductor pollicis brevis, first dorsal interosseous, and abductor digit minimi were prospectively performed in a cohort of 34 patients (77 muscles) with electromyography (EMG)-confirmed denervation, compared with 58 healthy control subjects. RESULTS: In control subjects, muscle thickness was highly reproducible [intraclass correlation coefficient (ICC) = 0.88-0.98], and echogenicity was moderately reproducible (ICC = 0.542-0.686). Age, gender, and body mass index influenced muscle thickness and echogenicity. Ultrasound changes in denervated muscles correlated with the severity of EMG abnormalities. A z-score cutoff of 0 identified denervated muscles with a sensitivity of 100% and 89% for echogenicity and muscle thickness, respectively. CONCLUSIONS: Hand muscle ultrasound provides a noninvasive method to quantify muscle denervation and may be useful as a screening tool before EMG studies.

A comparison of ultrasonographic and electrophysiologic 'inching' in ulnar neuropathy at the elbow.

OBJECTIVE: The present study aimed to clarify the relationship between structural ulnar nerve changes and electrophysiological nerve dysfunction in patients with ulnar neuropathy at the elbow (UNE). METHODS: High-resolution ultrasonography of the ulnar nerve was performed on 17 limbs with clinically and electrophysiologically confirmed UNE, and 52 control subjects at four standardised sites proximal and distal to the medial epicondyle (P2, P1, D1, D2), corresponding to segments of ulnar short-segment nerve conduction studies ("inching studies"). RESULTS: Ulnar nerve cross-sectional area (CSA) and hypoechoic fraction were significantly increased in patients with UNE immediately distal (D1) and proximal (P1) to the medial epicondyle (p<0.01). In patients with UNE, hypoechoic fraction was similar in asymptomatic and symptomatic limbs. Motor nerve conduction velocity across the elbow correlated with CSAmax and the maximum hypoechoic fraction (R=0.6, p<0.05). CSA and hypoechoic fraction of individual segments did not correlate with corresponding latencies on inching studies, but latencies across the D1 segment correlated with CSA at P1 (R=0.80, p<0.0001) and D2 (R=0.65, p<0.01). CONCLUSIONS: Sonographic abnormalities in UNE may not be maximal at the site of electrophysiological nerve dysfunction. SIGNIFICANCE: Sonographic abnormalities may reflect secondary pathophysiological changes in segments adjacent to regions of nerve compression.

Transient hyperckemia in the setting of neuromyelitis optica (NMO).

INTRODUCTION: Neuromyelitis optica (NMO) is characterized by inflammatory demyelinating lesions of the spinal cord and optic nerves from an autoimmune response against water channel aquaporin-4 (AQP4). We report 2 patients with transient hyperCKemia associated with NMO suggesting possible skeletal muscle damage. METHODS: Patient 1 was a 72-year-old man who presented with muscle soreness and elevated serum creatine kinase (CK) preceding an initial attack of NMO. Patient 2 was a 25-year-old woman with an established diagnosis of NMO who presented with diffuse myalgias, proximal upper extremity weakness, and hyperCKemia. Muscle biopsies were obtained for histopathologic evaluation, protein gel electrophoresis, immunofluorescence, and complement staining. RESULTS: In both patients the muscle showed only mild variation in fiber diameter. There were no inflammatory changes or muscle fiber necrosis, though there was reduced AQP4 expression and deposition of activated complement. CONCLUSIONS: Complement-mediated sarcolemmal injury may lead to hyperCKemia in NMO.

Dual reinnervation of biceps muscle after side-to-side anastomosis of an intact median nerve and a damaged musculocutaneous nerve.

Traumatic peripheral nerve injury can lead to significant long-term disability for previously healthy persons. Damaged nerve trunks have been traditionally repaired using cable grafts, but nerve transfer or neurotization procedures have become increasingly popular because the axonal regrowth distances are much shorter. These techniques sacrifice the existing nerve pathway, so muscle reinnervation depends entirely on the success of the repair. Providing a supplemental source of axons from an adjacent intact nerve by using side-to-side anastomosis might reinnervate the target muscle without compromising the function of the donor nerve. The authors report a case of biceps muscle reinnervation after side-to-side anastomosis of an intact median nerve to a damaged musculocutaneous nerve. The patient was a 34-year-old man who had sustained traumatic injury primarily to the right upper and middle trunks of the brachial plexus. At 9 months after the injury, because of persistent weakness, the severely damaged upper trunk of the brachial plexus was repaired with an end-to-end graft. When 8 months later biceps function had not recovered, the patient underwent side-to-side anastomosis of the intact median nerve to the adjacent distal musculocutaneous nerve via epineural windows. By 9 months after the second surgery, biceps muscle function had returned clinically and electrodiagnostically. Postoperative electromyographic and nerve conduction studies confirmed that the biceps muscle was being reinnervated partly by donor axons from the healthy median nerve and partly by the recovering musculocutaneous nerve. This case demonstrates that side-to-side anastomosis of an intact median to an injured musculocutaneous nerve can provide dual reinnervation of the biceps muscle while minimizing injury to both donor and recipient nerves.

Electrical brain events associated with awareness of errors.

OBJECTIVE: The neurophysiological correlates of mental activity and awareness are important to define, as they permit the objective study of these psychological phenomena. METHODS: In a choice reaction task, subjects were asked to respond to tone pips by extending their fingers and to make non-semantic vocalizations as soon as they became aware of any errors. RESULTS: In motor response-synchronized averages of instances in which subjects were aware of making errors, a biphasic cerebral potential occurred over the frontocentral scalp region 170 ms after the incorrect motor response and about 500 ms prior to any vocalization. It occurred 100 ms after the so-called error negativity (Ne), from which it was therefore distinguished. CONCLUSION: The recording of such activity may therefore provide an electrophysiological signature of perceptual awareness related to making errors. SIGNIFICANCE: Recording this potential may facilitate the objective study of awareness to errors in other experimental contexts.