Patient Experience Contributing to Outcomes of Laryngeal Botulinum Toxin Injection.

OBJECTIVES: Laryngeal Botulinum Toxin injection (LBTX) in the adductor musculature is the current therapy for Adductor Spasmodic Dysphonia. This study explores nonbiological factors that can affect the patient experience during this procedure and their association with better or worse self-reported effectiveness. METHODS: A 14 item survey was used to evaluate the patient experience in patients who had undergone LBTX in Mayo Clinic Jacksonville, Florida, during 2019. Information from the survey, previous medical history, and demographic data were collected, and a descriptive analysis was performed. RESULTS: Of the 36 patients who participated, the mean age was 65 years and a female predominance was found (66%). The average age at onset of symptoms was 57 years, and voice tremor was associated with 36.1% of patients. Preprocedure education was recognized as a factor affecting outcomes in 87% of patients; 11 patients reported that body position used during the injection could affect the results. Pain or stress experienced at the time of procedure was referred in one-third of patients as an influencing factor too. CONCLUSION: This study has shown that nonpharmacological factors such as education before the procedure, body position, pain, and stress sensation before LBTX may have a role in the botulinum toxin effect on Adductor Spasmodic Dysphonia patients. This study is the first to describe these variables qualitatively, and further studies may help to improve the patient experience and outcome of LBTX around the world.

Clinical neurophysiology of cranial nerve disorders.

Electrophysiologic techniques are available to measure many of the cranial nerves. The procedures can be done using equipment available in standard clinical neurophysiology laboratories. These studies can aid in localization of cranial nerve lesions as well help identify the underlying pathology and possibly aid in prognosis. The trigeminal pathways can be measured using the blink and masseter responses. The facial nerve is measured by the blink response and by direct facial stimulation; techniques such as lateral spread can identify specific abnormalities. The spinal accessory nerve is measured using nerve conduction techniques. Needle examination can be routinely performed on muscles innervated by cranial nerves V, VII, X, XI and XII. These studies reliably measure the functional integrity of cranial nerves and their central pathways. Intraoperative monitoring of the cranial nerves is useful in certain surgeries. This chapter reviews current techniques used to evaluate cranial nerves, emphasizing the methods available in most clinical neurophysiology laboratories.

Whole-exome sequencing for variant discovery in blepharospasm.

BACKGROUND: Blepharospasm (BSP) is a type of focal dystonia characterized by involuntary orbicularis oculi spasms that are usually bilateral, synchronous, and symmetrical. Despite strong evidence for genetic contributions to BSP, progress in the field has been constrained by small cohorts, incomplete penetrance, and late age of onset. Although several genetic etiologies for dystonia have been identified through whole-exome sequencing (WES), none of these are characteristically associated with BSP as a singular or predominant manifestation. METHODS: We performed WES on 31 subjects from 21 independent pedigrees with BSP. The strongest candidate sequence variants derived from in silico analyses were confirmed with bidirectional Sanger sequencing and subjected to cosegregation analysis. RESULTS: Cosegregating deleterious variants (GRCH37/hg19) in CACNA1A (NM_001127222.1: c.7261_7262delinsGT, p.Pro2421Val), REEP4 (NM_025232.3: c.109C>T, p.Arg37Trp), TOR2A (NM_130459.3: c.568C>T, p.Arg190Cys), and ATP2A3 (NM_005173.3: c.1966C>T, p.Arg656Cys) were identified in four independent multigenerational pedigrees. Deleterious variants in HS1BP3 (NM_022460.3: c.94C>A, p.Gly32Cys) and GNA14 (NM_004297.3: c.989_990del, p.Thr330ArgfsTer67) were identified in a father and son with segmental cranio-cervical dystonia first manifest as BSP. Deleterious variants in DNAH17, TRPV4, CAPN11, VPS13C, UNC13B, SPTBN4, MYOD1, and MRPL15 were found in two or more independent pedigrees. To our knowledge, none of these genes have previously been associated with isolated BSP, although other CACNA1A mutations have been associated with both positive and negative motor disorders including ataxia, episodic ataxia, hemiplegic migraine, and dystonia. CONCLUSIONS: Our WES datasets provide a platform for future studies of BSP genetics which will demand careful consideration of incomplete penetrance, pleiotropy, population stratification, and oligogenic inheritance patterns.

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

BACKGROUND: 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. METHODS: We present a patient with global developmental delay, hypotonia, myopathy, joint hypermobility, and multiple other systemic complaints that were noted early in life. Later she was found to have multiple bone deformities involving her spine, with severe scoliosis that was corrected surgically. She was also diagnosed with ophthalmoplegia, chronic hypercapnic respiratory failure, and hypertension. At 22 years of age she presented to the genetics clinic with a diagnosis of mitochondrial myopathy and underwent whole exome sequencing (WES). RESULTS: Whole exome sequencing revealed two novel compound heterozygous variants in RYR1 (c.7060_7062del, p.Val2354del and c.4485_4500del, p.Tyr1495X). CONCLUSION: Review of her clinical, pathologic, and genetic findings pointed to a diagnosis of a congenital myopathy with fiber-type disproportion.

Occurrence of Crohn's disease with Parkinson's disease.

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

Cryoglobulinemic vasculitis in a patient with CREST syndrome.

Cryoglobulinemic vasculitis is a rare entity. Although it has been reported in diffuse systemic sclerosis, it has not been reported in calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia (CREST) syndrome. We report a patient with cryoglobulinemic vasculitis with CREST syndrome who did not have typical clinical features of vasculitis. This 58-year-old woman presented with mild generalized weakness and a diagnosis of CREST syndrome, which included Raynaud's syndrome, dysphagia and telangiectasias. She was positive for serum cryoglobulins, which led to a sural nerve biopsy. The biopsy results were consistent with cryoglobulinemic vasculitis. Cryoglobulinemic vasculitis has not been previously reported in CREST syndrome to our knowledge. Additionally, the patient also had limited clinical symptoms. Our patient displays the importance of checking for cryoglobulins and obtaining a nerve biopsy when the serum is positive. Both of these diagnostic tests were integral for directing appropriate treatment for this patient.

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.

Popliteus muscle hemorrhage as a rare cause of a proximal tibial neuropathy.

Proximal tibial neuropathy is an uncommon focal mononeuropathy that is most often caused by trauma, ischemia, or neoplastic infiltration or compression of the tibial nerve. We report a patient who presented with a tibial neuropathy following a leg injury, which initially mimicked a lumbosacral radiculopathy but which was the result of a proximal tibial neuropathy. Electrophysiologic studies confirmed a proximal tibial neuropathy and MRI revealed a popliteus muscle hemorrhage with mass effect on the tibial nerve. Following conservative management the patient had little recovery of function after 15 months.

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.

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.

The effect of paired stimuli on blink reflex latencies in normal subjects.

INTRODUCTION: In this study we assessed the effect of paired stimuli on the latencies and amplitudes of the blink reflex. METHODS: Blink reflexes were performed with single and paired (5-ms interstimulus interval) stimuli in 47 patients. The changes in latencies between paired and single stimuli were calculated. RESULTS: Paired stimulation produced two types of R1 waveform morphologies: single- and double-peaked waveforms. Increases in R1 and contralateral R2 latencies with paired stimulation were significantly higher in those with single-peaked R1 responses compared to those with double-peaked R1 responses. CONCLUSIONS: Interpreting the blink reflex latencies using paired stimulation requires visualization of the R1 waveform morphology. A double-peaked R1 response requires no change in normal latency values, but the latency of a single-peaked R1 should be interpreted from the second shock artifact. The effect on the R2 latency is variable.

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.

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.

Electrophysiological evaluation of cranial neuropathies.

BACKGROUND: Cranial nerve abnormalities occur frequently in both focal and diffuse neurologic disorders and can be evaluated by electrophysiological techniques available in most clinical neurophysiology laboratories. REVIEW SUMMARY: The optic nerve is evaluated by visual evoked potentials. Measurements of latency, amplitude, and waveform morphology are especially useful in detecting demyelinating lesions. Brain stem auditory evoked potentials evaluate the auditory portion of the eighth cranial nerve. Using an auditory stimulus, a number of waveforms are generated, and changes in the normal patterns of response can detect abnormalities. Assessment of the trigeminal and facial nerves is done using a series of electrical stimulation techniques including the blink, masseter, and masseter inhibitory reflexes and facial motor nerve conduction studies. The blink reflex detects lesions of the first division of the trigeminal nerve and the facial nerve. The masseter reflex evaluates the third division of the trigeminal nerve. Changes in responses are measured and, using a combination of these techniques, localization of lesions at specific sites can be made. Accessory motor nerve conduction is useful not only in focal nerve injury, but repetitive stimulation on the accessory and facial nerves is used in diagnosing neuromuscular junction disorders. In addition, many of the voluntary muscles innervated by the cranial nerves are accessible to needle electrode examination, and evaluation can aid in identification of focal nerve lesions, as well as diagnosis in diffuse nerve and muscle disorders. CONCLUSION: Electrophysiological techniques offer reliable means of measuring the integrity of the cranial nerves and their central pathways.

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.