Phosphoglycerate mutase deficiency with tubular aggregates in a patient from Panama.

INTRODUCTION: Phosphoglycerate mutase deficiency (PGAM) is a rare metabolic myopathy that results in terminal block in glycogenolysis. Clinically, patients with PGAM deficiency are asymptomatic, except when they engage in brief, strenuous efforts, which may trigger myalgias, cramps, muscle necrosis, and myoglobinuria. An unusual pathologic feature of PGAM deficiency is the association with tubular aggregates. METHODS: We report an African-American patient from Panama with partial deficiency of PGAM who presented with asymptomatic elevation of creatine kinase levels and tubular aggregates on muscle biopsy. RESULTS: Muscle biopsies showed subsarcolemmal and sarcolemmal tubular aggregates in type 2 fibers. Muscle PGAM enzymatic activity was decreased and gene sequencing revealed a heterozygous mutation in codon 78 of exon 1 of the PGAM2 gene, which is located on the short arm of chromosome 7. CONCLUSIONS: PGAM deficiency has been reported in 14 patients, 9 of whom were of African-American ethnicity, and in 5 (36%) tubular aggregates were seen on muscle biopsy. Contrary to previously reported cases, our patient was initially asymptomatic. This further expands the PGAM deficiency phenotype.

Intraoperative laryngeal electromyography in children with vocal fold immobility: results of a multicenter longitudinal study.

OBJECTIVES: To determine whether laryngeal electromyography (LEMG) can predict recurrent laryngeal nerve function return in children and whether LEMG can aid in the management of vocal fold immobility (VFI). DESIGN: Prospective case series. SETTING: Tertiary pediatric aerodigestive centers. PATIENTS: Twenty-five children aged 14 days to 7 years at the time of first LEMG (mean age, 21.4 months) with VFI who underwent flexible fiberoptic laryngeal examination, intraoperative LEMG of the thyroarytenoid muscles, and 12-month follow-up. MAIN OUTCOME MEASURES: To compare results of LEMG with flexible fiberoptic laryngeal examination in children with vocal fold paresis and to determine if LEMG can predict vocal fold return. RESULTS: In children who had a patent ductus arteriosus ligation, the LEMG data suggest that if there is no activity 6 months after injury, then the nerve is unlikely to regain function. In 3 of 3 children with central causes of VFI, normal LEMG findings predicted return of nerve function 2 to 7 months before vocal fold movement on fiberoptic examination. Finally, in 3 of 3 children with idiopathic VFI, LEMG predicted return within 2 to 14 months of vocal folds with normal findings. CONCLUSIONS: Intraoperative LEMG is a safe, easy-to-use method for determining the likelihood of recurrent laryngeal nerve function return in children who have undergone patent ductus arteriosus ligation, in children with centrally correctable lesions, and in children with idiopathic VFI. More work is needed in the area of pediatric LEMG, but it is possible that LEMG data can be used to aid in management strategies and provide families with more information to make better informed decisions regarding their child's care.

Spontaneous and evoked laryngeal electromyography of the thyroarytenoid muscles: a canine model for intraoperative recurrent laryngeal nerve monitoring.

OBJECTIVES: We sought to determine the feasibility of performing spontaneous and evoked intraoperative laryngeal electromyography (L-EMG) using nerve monitoring equipment and to compare recording electrode configurations and methods of recurrent laryngeal nerve (RLN) stimulation in dogs. METHODS: Four beagles underwent crush injury of the left RLN, and 2 beagles underwent left RLN transection. Serial spontaneous and evoked L-EMG was recorded with the NIM-Response nerve monitoring system under sedation. Transesophageal, percutaneous, and direct open RLN stimulation was performed. Recordings of spontaneous and evoked responses were made with endotracheal tube surface electrodes and bipolar vocal fold needle electrodes. The L-EMG procedures were repeated every 1 to 2 weeks after injury, and intersubject and intertrial differences were evaluated. RESULTS: Low-amplitude motor unit action potentials, polyphasic potentials, fasciculations, and fibrillations were detected in injured animals with bipolar needle recording electrodes with this system of spontaneous L-EMG. The surface recording electrodes did not detect pathologic waveforms. Percutaneous needle stimulation of the RLN is possible at currents slightly higher than those used for direct stimulation. Consistent, discrete, transesophageal stimulation of the RLN could not be reliably performed. Recording evoked responses with needle electrodes generated sharper waveforms, facilitating calculation of latency and wave duration. Evoked L-EMG utilizing surface recording electrodes limited the intertrial and intersubject variability of evoked amplitude. CONCLUSIONS: Typical patterns of nerve injury can be detected with this system of intraoperative L-EMG in a canine model. Quantitative measures of amplitude, latency, and wave duration in healthy and injured canine RLNs may be determined with this system.

Serial electromyography of the thyroarytenoid muscles using the NIM-response system in a canine model of vocal fold paralysis.

OBJECTIVES: We sought to determine whether serial intraoperative laryngeal electromyography (L-EMG) or evoked L-EMG predicts vocal fold (VF) recovery following iatrogenic injury. METHODS: Six beagles were sedated, and bipolar needle electrodes were inserted into each thyroarytenoid (TA) muscle. Endotracheal tube surface electrodes were also placed. As the sedation lightened, L-EMG activity was recorded from all electrodes with an intraoperative nerve monitoring system. The neck was opened, and direct recurrent laryngeal nerve (RLN) stimulation was performed. Subsequently, 4 animals underwent crush injury of the left RLN,and 2 animals underwent nerve transection. The L-EMG procedures were repeated every 1 to 2 weeks until left VF motion was observed in the dogs that suffered RLN crush injury. At each time point, the neck was opened and both RLNs were stimulated. RESULTS: Fibrillation potentials were detected in all animals after RLN injury. A change to electrical silence was seen in the animals in the crush injury group that were evaluated during the week preceding VF recovery. Fibrillation potentials and VF immobility persisted in the transection group throughout the complete time course of these experiments. The first appearance of an evoked response coincided with or occurred after the return of left VF motion in the crush injury group. The threshold, latency, and amplitude differed from those of the controls and approached normal values over time. No response was detected in the transected nerves. CONCLUSIONS: The disappearance of fibrillations on intraoperative L-EMG was noted in the animals tested the week before the return of VF motion, and the return of motor unit action potentials was seen along with return of VF function. Evoked L-EMG was not helpful in predicting the return of VF mobility, but it may help quantify degrees of RLN injury and predict the speed of recovery.

Relapsing Guillain Barré Syndrome and nephrotic syndrome secondary to focal segmental glomerulosclerosis.

A 49-year-old man developed simultaneously a Guillain Barré Syndrome (GBS) and a nephrotic syndrome (NS). The patient relapsed twice, despite treatment with intravenous immunoglobulins (IVIg) after a full or partial recovery, and became resistant to IVIg. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS). He responded to plasmapheresis and corticosteroids with simultaneous recovery of his GBS and NS, suggesting a common pathogenesis of the two conditions.

Intraoperative laryngeal electromyography in children with vocal fold immobility: a simplified technique.

OBJECTIVES: The primary objective of this study was to determine whether a simplified technique for intraoperative laryngeal electromyography was feasible using standard nerve integrity monitoring electrodes and audiovisual digital recording equipment. Our secondary objective was to determine if laryngeal electromyography data provided any additional information that significantly influenced patient management. METHODS: Between February 2006 and February 2007, 10 children referred to our institution with vocal fold immobility underwent intraoperative laryngeal electromyography of the thyroarytenoid muscles. A retrospective chart review of these 10 patients was performed after institutional review board approval. RESULTS: Standard nerve integrity monitoring electrodes can be used to perform intraoperative laryngeal electromyography of the thyroarytenoid muscles in children. In 5 of 10 cases reviewed, data from laryngeal electromyography recordings meaningfully influenced the care of children with vocal fold immobility and affected clinical decision-making, sometimes altering management strategies. In the remaining 5 children, data supported clinical impressions but did not alter treatment plans. Two children with idiopathic bilateral vocal fold paralysis initially presented with a lack of electrical activity on one or both sides but went on to develop motor unit action potentials that preceded recovery of motion in both vocal folds. CONCLUSIONS: Our findings suggest that standard nerve monitoring equipment can be used to perform intraoperative laryngeal electromyography and that electromyographic data can assist clinicians in the management of complex patients. Additionally, there may be a role for the use of serial intraoperative measurements in predicting recovery from vocal fold paralysis in the pediatric age group.

Multifocal motor neuropathy with conduction block: Distribution of demyelination and axonal degeneration.

OBJECTIVE: Multifocal motor neuropathy with conduction block (MMN) is an immune-mediated neuropathy, characterized by progressive muscle weakness. Although demyelination is regarded as the underlying pathophysiologic mechanism of MMN, recently, it was reported that different pathophysiologic mechanisms were responsible for disease in the upper and lower limbs. Specifically, demyelination in the upper limbs and axonal loss in the lower limbs. Consequently, the aim of the present study was to assess, through clinical neurophysiology studies, whether different pathophysiologic mechanisms were occurring in the upper and lower extremities. Furthermore, we wanted to investigate whether the presence of conduction block (CB) correlated with axonal degeneration (AD), and to determine the electrophysiological abnormalities that correlate with muscle weakness. METHODS: We reviewed medical records of 18 patients with MMN for clinical features (using the Medical Research Council score and Guys Neurology Disability Scale) and neurophysiologic abnormalities (CB, AD prolongation of distal motor and F-wave latencies, and reduction of conduction velocity in the demyelinating range). RESULTS: Electrophysiological abnormalities deemed specific of demyelination were non-significantly different in the upper and lower extremities. The presence of axonal degeneration correlated significantly with conduction block (odds ratio 10.4, 95% CI 4.2-25.6), and both parameters correlated with muscle weakness (P<0.01). CONCLUSION: Our study suggests that the same pathophysiologic process occurs in the upper and lower extremity nerves. Moreover, one pathophysiologic process may be responsible for the development of CB and AD, and therefore muscle weakness. SIGNIFICANCE: The present study has established that both AD and CB occur in MMN, irrespective of extremity, and both correlate with muscle weakness.

Acute sensory neuronopathy as the presenting symptom of Sjögren's syndrome.

Sensory neuronopathy associated with Sjögren's syndrome (SS) usually has a subacute or chronic onset. We report the case of a 37-year-old woman who presented with an unusual hyperacute form of SS ganglionopathy. She initially developed paresthesias of her fingertips and rapidly became severely ataxic. Nerve conduction studies revealed abnormal sensory but normal motor functions. Lip biopsy showed findings consistent with SS. Sural nerve biopsy showed severe axonal loss. The patient showed modest improvement with immunosuppressive therapies.

Cervical nerve root stimulation. Part I: technical aspects and normal data.

OBJECTIVE: Cervical nerve root stimulation (CRS) is a technique of assessing the proximal segments of motor axons destined to upper extremity muscles. Few studies report normal values. The objective was to determine CMAP onset-latencies and CMAP amplitude, area, and duration changes in healthy controls for the abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps, and riceps muscles. In addition, to determine the tolerability of CRS, as measured by the visual analog scale (VAS). METHODS: We studied 21 healthy volunteers prospectively with CRS using four target muscles (APB, ADM, biceps, and triceps) bilaterally. Collision studies were used in all APB recordings. VAS was obtained in all subjects. RESULTS: Mean CMAP onset-latencies were: APB 14 +/- 1.5 ms; ADM 14.2 +/- 1.5 ms; biceps 5.4 +/- 0.6 ms; triceps 5.4 +/- 1.0 ms. Onset-latency significantly correlated with height for all nerves. The mean change in CMAP amplitude and area (%) between most distal stimulation and CRS was: APB reduction of 15.1 +/- 11.6 and 4.9 +/- 3.6%; ADM reduction of 21.1 +/- 10.7 and 17.2 +/- 8.8; biceps reduction of 10 +/- 11.5 and reduction of 8.7 +/- 6.8; triceps increase of 3.3 +/- 5.2 and 11.0 +/- 9.9% respectively. Mean CMAP duration change between most distal stimulation and CRS was: APB, increase of 20.4 +/- 7.4%; ADM, increase of 14.4 +/- 8.5%; biceps, increase of 13.9 +/- 10.8%; triceps, increase of 7.7 +/- 6.7%. The mean VAS score was 3.8 +/- 1.2, and all subjects completed the study. CONCLUSIONS: The present study establishes normative data and indicates that CRS is a well-tolerated technique. SIGNIFICANCE: The normal values may be used as reference data for the needle CRS technique in the assessment of proximal conduction abnormalities.

Multifocal motor neuropathy: decrease in conduction blocks and reinnervation with long-term IVIg.

BACKGROUND: Multifocal motor neuropathy with conduction blocks (MMNCB) is an immune-mediated motor neuropathy. Previous long-term IV immunoglobulin (IVIg) treatment studies have documented improvement in muscle strength and functional disability but revealed a concomitant increase in acute axonal degeneration (AD) and conduction block (CB). OBJECTIVE: To determine the long-term effects of IVIg therapy on clinical and neurophysiologic outcome measures in MMNCB patients responsive to IVIg. METHODS: The authors reviewed medical records of 10 patients with MMNCB for outcomes in muscle strength (Medical Research Council score), functional disability (Modified Rankin Disability score), CB, and AD. All patients had received IVIg (2g/kg in 5 days for 3 consecutive months), followed by monthly maintenance therapy. RESULTS: Patients were followed for an average of 7.25 years (range, 3.5 to 12 years). There was significant and sustained improvement in muscle strength and functional disability while on IVIg therapy. Furthermore, the authors found significant improvement in CB, decrease in AD, and evidence of reinnervation by the end of the follow-up period. CONCLUSION: Long-term IV immunoglobulin therapy improves muscle strength and functional disability, decreases the number of conduction blocks and the extent of axonal degeneration, and promotes reinnervation. These findings differ from previous reports of deterioration in neurophysiologic outcome measures. Comparison of the IV immunoglobulin regimen in those reports and this study shows that the authors' patients were treated with significantly higher IV immunoglobulin maintenance doses. These findings have implications for the long-term treatment of patients with multifocal motor neuropathy with conduction blocks.

Neurophysiologic findings in early acute inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND: Patients with early acute inflammatory demyelinating polyradiculoneuropathy (AIDP) may not meet the current neurophysiologic criteria. OBJECTIVE: To document neurophysiologic findings in early AIDP. METHODS: Clinical and neurophysiologic data from 38 AIDP patients, assessed within 10 days of symptom onset were reviewed. RESULTS: In addition to absent H reflexes and abnormal F-wave responses in the acute stage of AIDP, abnormalities of blink reflexes, upper limb sensory responses abnormalities with spared sural responses, presence of distal CMAP dispersion, and A-waves were frequently observed. Established demyelinating neurophysiologic parameters were infrequently seen. CONCLUSIONS: Abnormalities of H reflexes and F responses were most frequently noted in early AIDP. Additionally, distal temporal dispersion, prolonged or absent blink reflexes, and A-waves were often present in the acute stage of AIDP when classic diagnostic criteria of AIDP were not satisfied. SIGNIFICANCE: Neurophysiologic studies in early AIDP frequently reveal abnormalities that are not specific of primary demyelinating neuropathy.

Technology literature review: quantitative sensory testing.

The development of the personal computer has simplified the process of quantitating sensory thresholds using various testing algorithms. We reviewed the technical aspects and reproducibility of different methods to determine threshold for light touch-pressure, vibration, thermal, and pain stimuli. Clinical uses and limitations of quantitative sensory testing (QST) were also reviewed. QST is a reliable psychophysical test of large- and small-fiber sensory modalities. The results of QST are highly dependent on methodology and the full cooperation of the subject. QST has been shown to be reasonably reproducible over a period of days or weeks in normal subjects. The use of QST in research and patient care should be limited to instruments and their corresponding methodologies that have been shown to be reproducible. Literature data do not allow conclusions regarding the relative merits of individual QST instruments.

Atypical presentations of primary amyloid neuropathy.

Primary amyloidosis (AL) may be complicated by peripheral neuropathy in 15-35% of cases. We report on four patients with atypical neurological presentations of AL neuropathy, whose diagnoses were delayed due to varied clinical presentations. The clinical presentation included painful sensory neuropathy (two patients), mononeuropathy multiplex (one patient), and primary demyelinating polyneuropathy (one patient). The latter two types of presentation have not been reported previously. The diagnosis was established by fat pad biopsy in two patients, lymph node biopsy in one, and sural nerve biopsy in one. Two patients were treated with high-dose melphalan followed by stem cell rescue, and one was treated with oral melphalan and prednisone. All three cases experienced stabilization of neuropathic symptoms. We report these cases in order to raise awareness of the varied clinical presentation of AL neuropathy.