Kathleen D. Kennelly

De Novo Truncating FUS Gene Mutation as a Cause of Sporadic Amyotrophic Lateral Sclerosis

Mutations in the gene encoding fused in sarcoma (FUS) were recently identified as a novel cause of amyotrophic lateral sclerosis (ALS), emphasizing the genetic heterogeneity of ALS. We sequenced the genes encoding superoxide dismutase (SOD1), TAR DNA‐binding protein 43 (TARDBP) and FUS in 99 sporadic and 17 familial ALS patients ascertained at Mayo Clinic. We identified two novel mutations in FUS in two out of 99 (2.0%) sporadic ALS patients and established the de novo occurrence of one FUS mutation. In familial patients, we identified three (17.6%) SOD1 mutations, while FUS and TARDBP mutations were excluded. The de novo FUS mutation (g.10747A>G; IVS13‐2A>G) affects the splice‐acceptor site of FUS intron 13 and was shown to induce skipping of FUS exon 14 leading to the C‐terminal truncation of FUS (p.G466VfsX14). Subcellular localization studies showed a dramatic increase in the cytoplasmic localization of FUS and a reduction of normal nuclear expression in cells transfected with truncated compared to wild‐type FUS. We further identified a novel in‐frame insertion/deletion mutation in FUS exon 12 (p.S402_P411delinsGGGG) which is predicted to expand a conserved poly‐glycine motif. Our findings extend the mutation spectrum in FUS leading to ALS and describe the first de novo mutation in FUS.

Phrenic Nerve Palsy and Parsonage-Turner Syndrome

This report describes 2 symptomatic patients with phrenic nerve palsy due to Parsonage-Turner syndrome who were managed by diaphragmatic plication. The characteristics of the underlying syndrome are defined.

Acute onset of deep peroneal neuropathy during a golf game resulting from a ganglion cyst.

We report a case of sudden onset of deep peroneal neuropathy resulting from a ganglion cyst. Electrophysiology demonstrated a severe deep peroneal neuropathy with axonal loss and probably proximal conduction block. Magnetic resonance imaging demonstrated a mass arising from the proximal tibiofibular joint extending along the peroneal nerve. Surgical resection of the ganglion resulted in gradual improvement of strength. Peroneal nerve ganglia should be considered in the evaluation of patients with sudden painless foot drop.

Total laryngectomy in patients with advanced bulbar symptoms of amyotrophic lateral sclerosis

Our objectives were to 1) increase awareness of total laryngectomy (TL) as a treatment for complications of bulbar weakness in patients with amyotrophic lateral sclerosis (ALS) and outline specific surgical indications; 2) educate physicians about the surgical procedure, peri-operative course and benefits from having a TL; and 3) retrospectively review the clinical course of Mayo Clinic – Florida patients with ALS who had a TL. The method used was a retrospective review of patients recommended to undergo TL for advanced bulbar symptoms related to ALS at the Mayo Clinic in Jacksonville, Florida. Between January 1999 and September 2008, 15 patients with severe bulbar symptoms associated with ALS were recommended to undergo TL. Only five patients opted for the surgery. All patients were aphonic at time of surgery with a multitude of bulbar symptoms. Average surgical time was 114 min (range 87–162 min). No intraoperative complications were reported. All patients and caregivers were pleased with the results of the TL. In conclusion, TL is a relatively safe, quick and uncomplicated surgical procedure that should be considered earlier and more frequently in the treatment plan of patients with advanced bulbar symptoms due to ALS. We recommend considering TL in patients with aspiration problems who are unable to phonate intelligibly.

Defining normal duration for afterdischarges with repetitive nerve stimulation: A pilot study

The presence of afterdischarges on repetitive nerve stimulation may be useful to diagnose cramp fasciculation syndrome, however, the presence and normal duration of afterdischarges has not been well-defined in the normal population and individuals with other neuromuscular diseases. The aim of this pilot study was to describe the distribution of afterdischarge durations in normal controls and patients with peripheral neuropathy. The estimated seventy-fifth percentiles of the afterdischarge durations following tibial nerve repetitive nerve stimulation at 2, 5, 10, and 20 Hz were 315, 688, 745, and 928 milliseconds for 18 normal patients, and 143, 31, 323, and 542 milliseconds for 18 peripheral neuropathy patients respectively. Afterdischarge durations were similar in peripheral neuropathy patients and controls. These findings suggest that afterdischarge durations of more than 500 milliseconds are common in normal controls without subjective cramps and patients with peripheral neuropathy, with some durations beyond 1,000 milliseconds. Therefore, the presence of afterdischarges on repetitive nerve stimulation should be interpreted with caution when evaluating patients for hyperexcitable nerve syndromes.

SPONTANEOUS TIBIALIS ANTERIOR TENDON RUPTURE: A RARE CAUSE OF FOOT DROP

Tibialis anterior tendon (TAT) rupture is an uncommon musculoskeletal condition that is rarely encountered by neurologists.1 Most patients present with foot drop and pain and may be misdiagnosed as a peroneal mononeuropathy or L5 radiculopathy. Clinical recognition and distinction of this entity from other causes of foot drop are important for neurologists. We describe two patients with spontaneous TAT ruptures who presented for neurologic consultation for suspected peroneal neuropathies. ### Case 1. A 73-year-old man with a history of atrial fibrillation and hypertension was walking on his treadmill when he noted a painless “pop” in his right anterior ankle followed by “flopping” of his foot. A few days later, he noted swelling on the anterior aspect of his ankle and difficulty dorsiflexing his right foot. He denied back pain and bladder dysfunction. Neurologic examination demonstrated mild weakness in right ankle dorsiflexion with normal strength in all other muscles including toe extension and ankle eversion and inversion. There was swelling on the anterior surface of the right ankle (figure, A). The extensor hallucis longus and digitorum longus tendons were intact, but the TAT was not palpable …

Occurrence of Crohn's disease with Parkinson’s disease

We retrospectively investigated the co-occurrence of Crohns disease in a cohort of 876 patients with Parkinsons disease, based on the observation that LRRK2 is a shared genetic risk factor. We identified 2 patients with Crohns disease; this number was consistent with the number of cases expected in the general population.

Improving referring physicians' understanding of electromyography reports when qualifying radiculopathies: A need for standardized terminology

Electromyographic (EMG) reporting of radiculopathies is not standardized, and the terminology used in reports can be misinterpreted by referring physicians. Physicians who refer patients for EMG studies at the Mayo Clinic were surveyed about their understanding of 6 different EMG interpretations of an S1 radiculopathy. Of 45 responders, the terms “acute, active,” “chronic, inactive,” and “old” were interpreted consistently by 95%, 98%, and 84% of responders, respectively. Physicians had the most difficulty understanding the meaning of “chronic” in isolation, “chronic, active,” or “old with uncompensated denervation.” These findings suggest a need to educate referring physicians on the meaning of the terms used in EMG reports and to develop standard guidelines for qualifying radiculopathies. Based on our observations, guidelines for the reporting of radiculopathies have been adopted in the Mayo Clinic Florida EMG laboratory. Muscle Nerve 49: 129–130, 2014

Whole exome sequencing of a patient with suspected mitochondrial myopathy reveals novel compound heterozygous variants in RYR1

Pathogenic variants in ryanodine receptor 1 (RYR1, MIM# 180901) are the cause of congenital myopathy with fiber‐type disproportion, malignant hyperthermia susceptibility type 1, central core disease of muscle, multiminicore disease and other congenital myopathies.

Electrodiagnostic Approach to Cranial Neuropathies

This article is a general review of cranial nerve conduction studies, including techniques as well as interpretation of data. The needle examination of various cranial innervated muscles is also reviewed. The nerve conduction studies include the blink, masseter (jaw jerk), and masseter inhibitory reflexes, which evaluate the trigeminal (blink and jaw jerk) and facial nerves (blink), as well as trigeminal, facial, and spinal accessory motor stimulation. The needle examination techniques for certain voluntary muscles innervated by cranial nerves V, VII, X, XI, and XII are also described.