Electrophysiologic features of fibular neuropathy in childhood and adolescence.

INTRODUCTION: We studied patterns of nerve injury in pediatric common fibular (peroneal) neuropathy (CFN). METHODS: A retrospective analysis was performed on data from 53 children with CFN at a pediatric electromyography laboratory. RESULTS: Conduction block at the fibular head was present in 35% of patients. Deep fibular axonal loss was identified in 77%, while superficial fibular axonal loss was identified in 45%. The pathophysiology was predominantly axonal in 72%, mostly demyelinating in 6%, and mixed in 22%. Predominantly demyelinating lesions at the fibular head demonstrated sparing of the superficial fibular sensory nerve (P = 0.01, Fischer exact test). Predominantly axonal lesions had a moderate correlation between superficial and deep fibular axonal loss (Spearman r = 0.52; P = 0.0001). CONCLUSIONS: There is frequent axonal and fascicular injury in pediatric CFN, similar to adults. Deep and superficial fibular nerve involvements correlate in axonal lesions, whereas superficial fibular sensory fibers are often spared in demyelinating lesions. Muscle Nerve, 2016 Muscle Nerve 55: 693-697, 2017.

Referral and diagnostic trends in pediatric electromyography in the molecular era.

INTRODUCTION: Major advances in genetic analysis and neuroimaging have modified the traditional diagnostic approach for neuromuscular disorders. The purpose of this study was to investigate the role of electromyography (EMG) in the molecular era. METHODS: We retrospectively surveyed reports of all EMG studies performed at Boston Children's Hospital from 2001 through 2011. Data were collected on study numbers, patient ages, referring provider subspecialty, study indication, electrophysiological diagnosis, and study utility. RESULTS: A total of 2100 studies were performed. The volume increased from ~160 to ~250 studies/year. There was a trend toward studying older children. Neurologists, including neuromuscular specialists, constituted the major referral pool, whereas referrals from orthopedics increased steadily. Polyneuropathies followed by mononeuropathies were the most common indications and diagnoses. Fifty-seven percent of studies were normal. EMG provided meaningful information in 94% of cases. CONCLUSION: EMG continues to play a cardinal role in the diagnosis of pediatric neuromuscular disorders, although its practice paradigm is evolving.

Clinical correlates of Charcot-Marie-Tooth disease in patients with pes cavus deformities.

INTRODUCTION: Given its association with Charcot-Marie-Tooth disease (CMT), pes cavus is a common reason for referral to a neurologist. We investigated clinical features that may predict CMT in children with pes cavus. METHODS: In this study we retrospectively reviewed pes cavus patients referred to Boston Children's Hospital in the past 20 years. Patients were categorized as idiopathic or CMT, based on EMG/genetic testing, and their clinical features were compared. RESULTS: Of the 70 patients studied, 33 had idiopathic pes cavus, and 37 had genetically confirmed CMT. Symptoms of weakness, unsteady gait, family history of pes cavus and CMT, and signs of sensory deficits, distal atrophy and weakness, absent ankle jerks, and gait abnormalities were associated with CMT. CONCLUSIONS: In children with pes cavus, certain clinical features can predict CMT and assist in selection of patients for further, potentially uncomfortable (EMG) and expensive (genetic) confirmatory investigations.

Pediatric sciatic neuropathy associated with neoplasms.

Seven children with sciatic neuropathy associated with an underlying neoplasm are reported. Clinical presentation, electrophysiological data, imaging, pathology, and/or autopsy results are described. Pain and weakness, primarily foot drop, were the most common presenting symptoms. The mechanism of sciatic neuropathy was varied and included: nerve infiltration by the adjacent neoplasm (neuroblastoma, rhabdomyosarcoma, and leukemic or lymphomatous infiltration); an expanding, intrinsic neurogenic tumor (perineurioma); or intraoperative stretch injury (osteosarcoma resection). The prognosis for sciatic nerve recovery was good among children who survived their associated cancer. Three children died from the cancer or complications of treatment. One child with perineurioma remained clinically stable, and two children improved after treatment of their neoplasm.

Ocular myasthenia gravis in a senior population: diagnosis, therapy, and prognosis.

The objectives of this study were (I) to explore the prognosis of ocular myasthenia gravis (OMG) in patients with onset at age 70 years and above (i.e. senior persons); (2) to identify predictors of secondary generalization in this age group; and 3) to address the effects of immunotherapy on this population of patients. We performed a retrospective analysis of 39 patients with myasthenia gravis who presented with only ocular signs and symptoms after age 70 years. Generalized myasthenia gravis (GMG) developed in 12 OMG patients (31%). None of the GMG patients required ventilator assistance or a feeding tube. Of the 12 ocular patients progressing to GMG, only one (8%) received immunotherapy prior to generalization. Of those OMG patients who did not progress to GMG, 52% received immunomodulatory therapy. Our senior OMG patients had a prognosis comparable with those of the published data for younger individuals. Although the presence of increased acetylceholine receptor antibody titers and occasionally abnormal repetitive nerve stimulation were useful tools to diagnose OMG, no test was predictive of later generalization. Senior onset OMG patients who received immunotherapy less frequently developed GMG than those not so treated.

Sporadic late onset nemaline myopathy responsive to IVIg and immunotherapy.

Sporadic late onset nemaline myopathy (SLONM) is a progressive myopathy of indeterminate etiology and poor outcome. If associated with a monoclonal gammopathy, SLONM carries a more unfavorable prognosis. Immunotherapy was unsuccessful. We report two HIV-negative SLONM/monoclonal gammopathy patients who improved following intravenous immunoglobulin (IVIg) treatment alone or in combination with immunosuppressant agents. This favorable response to treatment suggests that a dysimmune mechanism is operative in some SLONM individuals. We suggest that IVIg deserves initial consideration for SLONM therapy.

Pediatric monomelic amyotrophy: evidence for poliomyelitis in vulnerable populations.

Pediatric monomelic amyotrophy may present a diagnostic challenge. This is particularly true for immigrant or adopted children who have little or no available medical history. We present clinical and electrophysiological data from 11 children with monomelic amyotrophy who had electrophysiological evidence of a unilateral or profoundly asymmetric motor neuronopathy. The cause of amyotrophy in each case is most consistent with prior: (1) wildtype poliovirus myelitis; (2) "polio-like" virus myelitis, or (3) vaccine associated paralytic poliomyelitis.

Electrophysiologic Features of Radial Neuropathy in Childhood and Adolescence.

BACKGROUND: We analyzed the clinical and electrophysiologic patterns of nerve injury in pediatric patients with radial neuropathy. METHODS: This is a retrospective analysis of 19 children and adolescents with radial neuropathy. RESULTS: The mean subject age was 12 years (range one month to 19 years), 56% were female, and 53% had traumatic etiologies. Weakness in the finger and wrist extensors was the prevailing complaint (82%). Predominant localization was at the posterior interosseous nerve (37%), followed by the radial nerve below the spiral groove (32%), the radial nerve at the spiral groove (26%), and the radial nerve above the spiral groove (5%). Extensor indicis proprius compound muscle action potential amplitude was reduced in 86% of cases when tested, with a median axon loss estimate of 78%. The radial sensory nerve action potential amplitude was reduced in 53% of all cases, and in 83% of cases affecting the main radial trunk with a median axon loss estimate of 100%. For neuropathy affecting the main radial trunk, there was a high correlation of extensor indicis proprius median axon loss estimate and radial sensory nerve action potential median axon loss estimate (r = 0.72, P = 0.02). Neurogenic changes were seen in the extensor indicis proprius, extensor digitorum communis, extensor carpi radialis, and brachioradialis in 88%, 94%, 60%, and 44% of cases, respectively. Pathophysiology was demyelinating in 10%, axonal in 58%, and mixed in 32%. CONCLUSIONS: In contrast to adults, where localization at the spiral groove predominates, radial neuropathy in children and adolescents is commonly localized at the posterior interosseous nerve or at the distal main radial trunk. Pediatric radial neuropathy is frequently of traumatic etiology and axonal pathophysiology.

Electrophysiologic features of ulnar neuropathy in childhood and adolescence.

OBJECTIVE: To analyze patterns of nerve injury in pediatric ulnar neuropathy (PUN). METHODS: Retrospective analysis of 49 children with PUN. RESULTS: Sensory loss in digit V was the prevailing complaint (89%). Predominant localization was at the elbow (55%). Diminished ulnar SNAP was the most common abnormality (71%) with median axon loss estimate (MAXE) of 62%. Dorsal ulnar cutaneous (DUC) sensory nerve action potential (SNAP) was reduced in 55% with MAXE of 43%. Abductor digiti minimi (ADM) and first dorsal interosseous (FDI) compound muscle action potential (CMAP) were reduced half of the time, with MAXE of 30% and 28% respectively. There was high correlation between ulnar sensory MAXE and ADM MAXE (r=0.76, p<0.0001), FDI MAXE (r=0.81, p<0.0001) and DUC MAXE (r=0.60, p=0.0048). Neurogenic changes were seen in the ADM, FDI, flexor carpi ulnaris (FCU) and flexor digitorum profundus IV (FDP IV) in 79%, 77%, 25% and 35% respectively. Pathophysiology was demyelinating in 27%, axonal in 59% and mixed in 14%. CONCLUSIONS: In proximal axonal lesions, sensory fibers to digit V and motor fibers to distal muscles are predominantly affected, whereas in demyelinating lesions, slowing occurs twice as frequently as conduction block. SIGNIFICANCE: There is frequent axonal and fascicular injury in PUN.

Severe ataxia, myelopathy, and peripheral neuropathy due to acquired copper deficiency in a patient with history of gastrectomy.

BACKGROUND: In animal studies, copper absorption has been demonstrated to occur in the proximal gut via duodenal enterocytes. Acquired copper deficiency is known as "swayback" in ruminant animals and Menkes' disease in humans. Copper is an essential micronutrient necessary for the hematologic and neurologic systems. Acquired copper deficiency in humans has been described, causing a syndrome similar to the subacute combined degeneration of vitamin B(12) deficiency. METHODS: This is a single case report. Our patient developed a neurologic constellation of ataxia, myelopathy, and peripheral neuropathy similar to vitamin B(12) deficiency many years after gastrectomy for severe peptic ulcer disease. The patient was maintained for decades with enteral feedings via jejunostomy that provided the recommended dietary allowance (RDA) for copper. RESULTS: Copper deficiency was suspected, identified, and treated. Over 3 months of follow-up, serum copper levels increased from 4 microg/dL to 20 microg/dL (70-150 microg/dL), and ceruloplasmin increased from 6 mg/dL to 8 mg/dL (14-58 mg/dL). During this short time of follow-up, the patient has had no further progression of his neurologic symptoms. CONCLUSIONS: Ataxia and myelopathy secondary to acquired copper deficiency are rare complications of major gastric resection. This is quite similar to the syndrome of vitamin B(12) deficiency. Vitamin B(12) repletion does not improve symptoms. Bariatric procedures such as gastric bypass surgery result in a similar functional anatomy of the proximal gut and may place more patients at increased risk. Early recognition and therapy with oral or parenteral copper may lead to a decrease in both neurologic and hematologic consequences.

Thalidomide neuropathy in childhood.

Thalidomide was withdrawn from world markets in 1961 following recognition of its teratogenic effects. More recently, however, thalidomide treatment has been reintroduced to adult and paediatric practice for a variety of dermatologic, immunologic, rheumatologic and neoplastic disorders. Neuropathy is a significant side effect of thalidomide therapy, which may limit its clinical use. We report four cases of sensorimotor axonal neuropathy in children aged 10-15 years, treated with thalidomide for myxopapillary ependymoma, Crohn's disease and recurrent giant aphthous ulceration. Thalidomide neuropathy is often associated with proximal weakness and may progress even after discontinuation of treatment, in the phenomenon of 'coasting'. Children treated with thalidomide should undergo regular neurophysiologic studies in order to detect presymptomatic or progressive peripheral neuropathy.

Paediatric mononeuritis multiplex: a report of three cases and review of the literature.

Mononeuritis multiplex results from disease processes causing multifocal injury to the peripheral nerves, with or without involvement of one or more cranial nerves. Most reported cases of paediatric mononeuritis multiplex have been related to autoimmune disorders. We present clinical and neurophysiologic findings in three cases of multiple mononeuropathy occurring in adolescence, with onset at ages 16, 17 and 13 years. Two of these cases were related to systemic vasculitis, one possibly representing a paediatric case of non-systemic vasculitis. Sural nerve biopsy confirmed the diagnosis of vasculitis in one patient with systemic lupus erythematosus, but was non-diagnostic in another case. Mononeuritis multiplex is an extremely uncommon form of acquired peripheral neuropathy in childhood. We discuss the differential diagnosis and review previous descriptions of this rare condition.

Current therapeutic strategies for patients with polyneuropathies secondary to inherited metabolic disorders.

Supportive care, symptomatic treatment, and patient education should be provided for patients with inherited or acquired polyneuropathies. In addition, specific treatment is available for many of the acquired polyneuropathies. Genetic counseling is valuable for many patients with inherited polyneuropathies, but only rarely is specific treatment an option for these patients. However, specific treatments are available for many of the rare and devastating systemic disorders associated with polyneuropathies. Thus, clinicians must promptly diagnose these inherited disorders so that specific treatment may be initiated. The clinical features of these rare inherited disorders are emphasized.

Neuromuscular problems of the critically ill neonate and child.

This review presents insights gained over 24 years of clinical and laboratory evaluations of children, newborn to 18 years of age, who present with acute weakness in the intensive care setting. The differential diagnosis of neuromuscular disorders in these cases begins with recognition of three categories-the infant and toddler, the older child and adolescent, and the child with critical illness-within which predisposition to specific disorders may be identified. Disorders originating from anterior horn cell, peripheral nerve, neuromuscular junction, and muscle cell are discussed with emphasis on presentation and electrophysiologic findings. Nerve conduction studies, electromyography, electroencephalography, cerebrospinal fluid analysis, and magnetic resonance imaging each play important diagnostic roles in the differentiation of neuromuscular disorders in the critically ill child. Case studies suggest the wide range of presentations these disorders may make to the pediatrician or pediatric neurologist.

Lambert-Eaton syndrome, an unrecognized treatable pediatric neuromuscular disorder: three patients and literature review.

BACKGROUND: Lambert-Eaton myasthenic syndrome, a presynaptic neuromuscular junction autoimmune disorder, rarely occurs in children. Patients typically present with proximal lower extremity weakness with areflexia. METHODS: We report three children presenting between ages 9 and 10 years diagnosed with Lambert-Eaton myasthenic syndrome 2 years, 1 year, and 5 months later, respectively. Their clinical attributes are correlated with nine other pediatric Lambert-Eaton myasthenic syndrome patients found in our literature review. RESULTS: These patients were identified as having Lambert-Eaton myasthenic syndrome during their evaluation for proximal weakness. Low-amplitude compound muscle action potentials classically facilitating >100% with voluntary exercise and/or 50 Hz stimulation were essential to diagnosis. Three of the 12 children had associated malignancies, two of them had lymphoproliferative disorders with onset of symptoms more rapid than the rest, and the third had neuroblastoma. The nine nonparaneoplastic Lambert-Eaton myasthenic syndrome patients responded to immunomodulatory therapy with close return to their baseline function. Complete remission no longer necessitating medication was reported in two patients. Follow-up up to 17 years was available on two patients previously reported. CONCLUSION: Lambert-Eaton myasthenic syndrome is a diagnosis that must be considered in children presenting with unidentified proximal muscle weakness. In most children, Lambert-Eaton myasthenic syndrome is a primary autoimmune disorder that is treatable. Nevertheless, a search for malignancy is recommended.

Childhood chronic inflammatory demyelinating polyradiculoneuropathy: combined analysis of a large cohort and eleven published series.

The clinical presentation, disease course, response to treatment, and long-term outcome of thirty childhood chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients are presented representing the largest cohort reported to date. Most children (60%) presented with chronic (>8-weeks) symptom-onset while a smaller proportion showed sub-acute (4-8 weeks) or acute (''GBS-like''; <4 weeks) onset of disease. No gender predilection was observed. The majority of patients had a relapsing (70%) versus a monophasic (30%) temporal profile. Most received initial IVIG monotherapy; 80% showing a good response. Long-term follow-up (mean=3.8 years) was available for 23 patients; 45% were off all immunomodulatory medications, demonstrating no detectable (55%) or minimal (43%) clinical deficits. Our data were compared with 11 previously published childhood CIDP series providing a comprehensive review of 143 childhood CIDP cases. The combined initial or first-line treatment response across all studies was favourable for IVIG (79% patients) and corticosteroids (84% patients). Response to first-line plasma exchange was poor (only 14% patients improved) although it may offer some transient or partial benefit as an adjuvant or temporary therapy for selected patients. The combined long-term outcome of our cohort and the literature reveals a favourable prognosis for most patients. The combined modified Rankin scale decreased from 3.7 (at presentation) to 0.7 (at last follow-up). This review provides important data pertaining to clinical course, treatment response and long-term outcome of this relatively uncommon paediatric autoimmune disease.

Childhood onset of stiff-man syndrome.

IMPORTANCE: Reports of pediatric-onset stiff-man syndrome (SMS) are rare. This may be an underrecognized disorder in child neurology practice. OBJECTIVE: To describe patients with disorders in the SMS spectrum beginning in childhood. DESIGN, SETTING, AND PARTICIPANTS: This study was a medical record review and serological evaluation conducted at child and adult neurology clinics at the Mayo Clinic, Rochester, Minnesota. Systematic review of the literature was conducted of patients who presented from 1984-2012 with onset of symptomatic SMS occurring at age 18 years or younger. MAIN OUTCOMES AND MEASURES: Response to symptomatic and immunotherapies, patient and physician reported, including modified Rankin scale. RESULTS: We identified 8 patients with childhood-onset SMS, representing 5% of patients with SMS evaluated at Mayo Clinic during a period of 29 years (4 were girls). The median age at symptom onset was 11 years (range, 1-14 years). The diagnosis in 3 patients was not established until adulthood (median symptom duration at diagnosis, 14 years; range, 0-46 years). The phenotypes encountered were: classic SMS (n = 5, involving the low back and lower extremities), variant SMS (n = 2, limited to 1 limb [with dystonic posture] or back), and progressive encephalomyelitis with rigidity and myoclonus (n = 1). Initial misdiagnoses included functional movement disorder (n = 2), generalized dystonia and parkinsonism (n = 1), and hereditary spastic paraparesis (n = 1). Six patients had 1 or more coexisting autoimmune disorders: type 1 diabetes mellitus (n = 4), thyroid disease (n = 2), and vitiligo (n = 2). Serologic study results revealed glutamic acid decarboxylase 65-IgG in all cases (median value, 754 nmol/L; range, 0.06-3847 nmol/L; normal value, ≤ 0.02 nmol/L) and glycine receptor antibody in 3 cases. Improvements were noted with symptomatic therapy (diazepam, 6 of 6 patients treated, and oral baclofen, 3 of 3 treated) and immunotherapy (intravenous immune globulin, 3 of 4 treated and plasmapheresis, 3 of 4 treated). The 3 patients with glycine receptor antibody all improved with immunotherapy. At last follow-up, 4 patients had mild or no symptoms, but 4 had moderate or severe residual symptoms and required maintenance symptomatic therapy (n = 5) and immunotherapy (n = 4). Ten of 12 pediatric SMS cases identified by literature review had a severe whole-body phenotype resembling progressive encephalomyelitis with rigidity and myoclonus. CONCLUSIONS AND RELEVANCE: Childhood-onset SMS is a rare but underrecognized and treatable disorder. Serological and electrophysiological testing aid diagnosis.

The spectrum of myotonic and myopathic disorders in a pediatric electromyography laboratory over 12 years.

This study assessed the spectrum of disorders associated with electrophysiologic myotonia in a pediatric electromyography laboratory. Records of 2234 patients observed in the Electromyography Laboratory at Boston Children's Hospital from 2000-2011 were screened retrospectively for electrophysiologic diagnoses of myotonia and myopathy. Based on electromyography, 11 patients manifested myotonic discharges alone, eight exhibited both myotonic discharges and myopathic motor unit potentials, and 54 demonstrated myopathic motor unit potentials alone. The final diagnoses of patients with myotonic discharges alone included myotonia congenita, paramyotonia congenita, congenital myopathy, and Pompe disease (acid maltase deficiency). The diagnoses of patients with both myotonic discharges and myopathic motor unit potentials included congenital myopathy and non-Pompe glycogen storage diseases. Myotonic discharges are rarely observed in a pediatric electromyography laboratory, but constitute useful findings when present. The presence or absence of concurrent myopathic motor unit potentials may help narrow the differential diagnosis further.

Brachial plexopathy and nonaccidental injury: role of the neurologist.

Child neurologists must remain vigilant to the possibility of nonaccidental injury. Just as clinicians have become accustomed to considering potential abuse or neglect in children presenting with a head injury or skeletal trauma, physical abuse must also be considered when children present with lesions at other sites of the neuraxis, as illustrated by this child's brachial plexopathy. Key elements from the history can assist clinicians in differentiating accidental events from nonaccidental injuries secondary to abuse or neglect. We report a toddler who presented with a recurrent brachial plexopathy due to nonaccidental injury. Her parents initially denied the occurrence of any significant trauma. Furthermore, her diagnosis was complicated by the identification of concomitant, but unrelated lead toxicity. In this case, the vague and inconsistent parental history, plexopathy recurrence, and identification of a fracture all heightened suspicion of child abuse.

Sensory polyneuropathy associated with paclitaxel-eluting coronary stent.

Paclitaxel is a microtubule-stabilizing chemotherapeutic agent used in ovarian and breast cancer; its principal adverse effect is sensory neuropathy. We describe the occurrence of sensory polyneuropathy after multiple paclitaxel-eluting stents in a patient who may have sub-clinical Sjogrens syndrome.