Electrodiagnostic features of acute paralytic poliomyelitis associated with West Nile virus infection

West Nile virus (WNV) infection is a potentially fatal disease, with meningoencephalitis being its most common neurological manifestation. Guillain-Barré syndrome (GBS) has also been described, but acute paralytic poliomyelitis has only recently been recognized. We report the clinical and electrodiagnostic findings of five patients with WNV infection, who presented with acute paralytic poliomyelitis. Three patients manifested focal asymmetrical weakness, and two had rapid ascending quadriplegia mimicking GBS. Electrodiagnostic studies during the acute illness showed normal sensory nerve action potentials, compound motor action potentials of normal or reduced amplitude, and no slowing of nerve conduction velocities. Depending on the timing of the examination, fibrillation potentials were widespread, including in those with focal weakness. Cervical magnetic resonance imaging in one patient showed abnormal T2-weighted signals in the spinal cord gray matter. On follow-up, signs of clinical improvement were seen in one patient, whereas two remained quadriplegic and ventilator-dependent 5 months after the onset. This report highlights the value of the electrodiagnostic studies in the diagnosis and prognosis of focal or generalized weakness due to acute paralytic poliomyelitis associated with WNV infection.     

West Nile virus and "poliomyelitis"

West Nile virus (WNV) has recently been associated with a syndrome of acute flaccid paralysis. Most cases of WNV-associated weakness have clinical, histopathologic, and electrophysiologic characteristics indistinguishable from those of poliomyelitis caused by infection with poliovirus. There is debate about the nomenclature of this manifestation of WNV infection. An historical perspective of the term "poliomyelitis" suggests that the term "WNV poliomyelitis" seems appropriate, but members of the neurologic and infectious disease communities should engage in discussion regarding the terminology of this syndrome.     

Delayed-onset and recurrent limb weakness associated with West Nile virus infection

Human neurologic illness following infection with West Nile virus (WNV) may include meningitis, encephalitis, and acute flaccid paralysis (AFP). Most WNV-associated AFP is due to involvement of the spinal motor neurons producing an anterior (polio)myelitis. WNV poliomyelitis is typically characterized by acute and rapidly progressing limb weakness occurring early in the course of illness, which is followed by death or clinical plateauing with subsequent improvement to varying degrees. We describe four cases of WNV poliomyelitis in which the limb weakness was characterized by an atypical temporal pattern, including one case with onset several weeks after illness onset, and three cases developing relapsing or recurrent limb weakness following a period of clinical plateauing or improvement. Delayed onset or recurrent features may be due to persistence of viral infection or delayed neuroinvasion with delayed injury by excitotoxic or other mechanisms, by immune-mediated mechanisms, or a combination thereof. Further clinical and pathogenesis studies are needed to better understand the mechanisms for these phenomena. Clinicians should be aware of these clinical patterns in patients with WNV poliomyelitis.     

Subacute brachial diplegia associated with West Nile virus myelitis

Introduction: Brachial diplegia is a clinical term used to describe weakness restricted to the upper extremities. We report a case of brachial diplegia associated with West Nile virus infection. Methods: A 48‐year‐old man developed severe painless bilateral upper extremity weakness within a few weeks of a flu‐like illness. Results: Clinical examination revealed marked periscapular, shoulder girdle, and humeral muscle atrophy and bilateral scapular winging, with near symmetrical bilateral hypotonic upper extremity weakness. This was associated with clinical signs of an encephalomyelopathy without cognitive or sensory deficits. Electrophysiological studies demonstrated a subacute disorder of motor neurons, their axons or both, involving the cervical and thoracic myotomes, with ongoing denervation. Serological studies confirmed recent West Nile virus (WNV) infection. Gradual improvement occurred following conservative supportive therapies. Conclusions: Progressive brachial diplegia is a rare neuromuscular presentation of WNV neuroinvasive disease. This case report adds to the clinical spectrum of WNV‐induced neurologic sequelae. Muscle Nerve 45: 900‐904, 2012     

West nile virus infection and myasthenia gravis

Introduction: Viruses are commonly cited as triggers for autoimmune disease. It is unclear if West Nile virus (WNV) initiates autoimmunity. Methods: We describe 6 cases of myasthenia gravis (MG) that developed several months after WNV infection. All patients had serologically confirmed WNV neuroinvasive disease. None had evidence of MG before WNV. Results: All patients had stable neurological deficits when they developed new symptoms of MG 3 to 7 months after WNV infection. However, residual deficits from WNV confounded or delayed MG diagnosis. All patients had elevated acetylcholine receptor (AChR) antibodies, and 1 had thymoma. Treatment varied, but 4 patients required acetylcholinesterase inhibitors, multiple immunosuppressive drugs, and intravenous immune globulin or plasmapheresis for recurrent MG crises. Conclusions: The pathogenic mechanism of MG following WNV remains uncertain. We hypothesize that WNV‐triggered autoimmunity breaks immunological self‐tolerance to initiate MG, possibly through molecular mimicry between virus antigens and AChR subunits or other autoimmune mechanisms. Muscle Nerve 49 : 26–29, 2014     

Acute‐onset chronic inflammatory demyelinating polyneuropathy: An electrodiagnostic study

Introduction: Acute‐onset chronic inflammatory demyelinating polyneuropathy (A‐CIDP) is an increasingly recognized CIDP subtype. Differentiating A‐CIDP from Guillain–Barré syndrome (GBS) is challenging but important, because there are different treatment outcomes. Methods: We report 3 patients with A‐CIDP who were initially diagnosed with severe GBS but were later confirmed to have CIDP based on their clinical course and electrodiagnostic (EDx) studies. We also report on the long‐term treatment of these patients and review the literature on EDx studies in this syndrome. Results: Three patients were initially diagnosed with GBS and responded to treatment. However, all 3 had arrest in improvement or deterioration during their rehabilitation phases. EDx studies showed prominent demyelinating changes many months after the initial presentation. All responded very well to immunotherapy. Conclusion: Although several features may suggest the diagnosis of A‐CIDP at initial presentation, close follow‐up of GBS patients during the recovery phase is also needed for accurate diagnosis. EDx studies may distinguish patients with A‐CIDP from GBS patients. Muscle Nerve 52 : 900–905, 2015     

Neurological manifestations of West Nile virus infection

BACKGROUND: Over the past four years, West Nile virus (WNV) has become a significant health issue in North America. In 2002, WNV infection made its first appearance in the human population in Canada. METHODS: Patients who presented to the University Health Network and Mount Sinai Hospital in Toronto with neurological disease attributed to WNV infection were identified and followed by the neurology service. Clinical features and results of laboratory, electrodiagnostic, radiological and pathological studies are presented. RESULTS: In August and September 2002, 26 patients were admitted with WNV infection; 14 presented with neurological illness. Encephalitis was the most common presentation (11 patients). Eleven patients developed neuromuscular disease; two at presentation and nine after encephalitis. While the majority had a motor process that localized to the anterior horn cell and/or motor neuron, two patients had evidence of a demyelinating neuropathy and one a sensorimotor axonal neuropathy. Less common manifestations included rhombencephalitis, ataxia, myelopathy and parkinsonism. Death occurred in four patients; two > 75 years of age, and two who were immunocompromised. CONCLUSIONS: The most common neurological manifestation of WNV infection was encephalitis with subsequent neuromuscular involvement. The diversity of clinical and pathological findings, however, suggests widespread involvement of the central and peripheral nervous system. A poorer prognosis for neurological recovery and overall survival was seen in older and immunocompromised patients.     

Clinical characteristics and functional outcome of patients with West Nile neuroinvasive disease in Serbia

Neurologic manifestations are prominent characteristic of West Nile virus (WNV) infection. The aim of this article was to describe neurological manifestations in patients with WNV neuroinvasive disease and their functional outcome at discharge in the first human outbreak of WNV infection in Serbia. The study enrolled patients treated in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia in Belgrade, with serological evidence of acute WNV infection who presented with meningitis, encephalitis and/or acute flaccid paralyses (AFP). Functional outcome at discharge was assessed using modified Rankin Scale (mRS) and Barthel index. Fifty-two patients were analysed. Forty-four (84.6 %) patients had encephalitis, eight (15.4 %) had meningitis, and 13 (25 %) had AFP. Among patients with AFP, 12 resembled poliomyelitis and one had clinical and electrodiagnostic findings consistent with polyradiculoneuritis. Among patients with encephalitis, 17 (32.7 %) had clinical signs of rhombencephalitis, and eight (15.4 %) presented with cerebellitis. Respiratory failure with subsequent mechanical ventilation developed in 13 patients with WNE (29.5 %). Nine (17.3 %) patients died, five (9.6 %) were functionally dependent (mRS 3–5), and 38 (73.1 %) were functionally independent at discharge (mRS 0–2). In univariate analysis, the presence of AFP, respiratory failure and consciousness impairment were found to be predictors of fatal outcome in patients with WNV neuroinvasive disease (p < 0.001, p < 0.001, p = 0.018, respectively). The outbreak of human WNV infection in Serbia caused a notable case fatality ratio, especially in patients with AFP, respiratory failure and consciousness impairment. Rhombencephalitis and cerebellitis could be underestimated presentations of WNV neuroinvasive disease.     

Glial S100B is elevated in serum across the spectrum of West Nile virus infection

Introduction: We previously reported that protein biomarkers of neuronal death and glial pathology were elevated in the cerebrospinal fluid of patients with West Nile virus (WNV) infection, including WNV fever. Therefore, we hypothesized that the glial biomarker S100B would also be elevated in serum across the spectrum of WNV disease. Methods: Serum levels of S100B were measured by enzyme‐linked immunoassay (ELISA) in 90 WNV patients (35 with neuroinvasive disease and 55 with WNV fever) and compared with 34 healthy controls. Results: Serum S100B was significantly higher in patients (median 0.17 ng/ml) than in controls (0.09 ng/ml, P < 0.0001). Serum S100B was elevated in 16 cases (46%) with neuroinvasive disease and in 19 cases (35%) with WNV fever. Conclusions: The increase in serum S100B reaffirms pathological changes across the spectrum of WNV disease. The elevated S100B in over one third of WNV fever cases implies that neuroinvasion occurs in a much greater proportion of patients than anticipated by clinical and epidemiological data. Muscle Nerve 45: 826–830, 2012     

Anti‐Borna disease virus antibody responses in psychiatric patients: Long‐term follow up

Aim: Data suggesting a pathogenetic role for Borna disease virus (BDV) in neuropsychiatric diseases are still inconclusive and it is unknown whether humans become persistently infected or clear the virus infection. The aim of the present study was therefore to investigate long‐term BDV‐specific antibody responses in psychiatric patients in order to gain new insights into human BDV infection and its pathogenicity. Methods: BDV‐specific antibody titers and associations with clinical conditions were studied retrospectively in 94 seropositive patients with schizophrenia (n = 46), affective disorders (n = 19) and other psychiatric disorders (n = 29) who had been repeatedly tested for the presence of BDV‐specific antibodies on indirect immunofluorescence assay between 1985 and 2006. Long‐term titer dynamics were studied in 46 patients followed up for a period of >36 months. Results: A total of 25 of these 46 patients (54.3%) had persistent seropositivity, whereas seroreversion from positive to negative was observed in 21 (45.7%). Patients in the early course of schizophrenia had lower antibody titers compared to patients in the advanced course (P = 0.017), while a higher proportion of patients in the early course had titer increases (P < 0.05). There were no significant differences in antibody titers between patient subgroups with clinically stable and acute psychiatric disorders. Conclusion: Persistent seropositivity in a subgroup of psychiatric patients in the long‐term analysis suggests chronic BDV infection in humans.     

Diffuse age‐related lumbar mri changes confound diagnosis of single (L5) root lesions

Introduction: L5 radiculopathy has characteristic clinical and electrodiagnostic features including: radicular pain; weakness or denervation of hip abductors, ankle dorsiflexors, and inverters; and pre‐ganglionic dorsal foot sensory loss. It is unknown how often patients with this distinctive clinical–electrodiagnostic presentation have isolated L5‐root compression on neuroimaging or more widespread, possibly age‐related, lumbar neuroforaminal or spinal stenosis. Methods: A study‐blinded neuroradiologist quantitated lumbosacral neuroforaminal, lateral recess, and spinal stenosis in 26 consecutive patients with unilateral, clinically and EMG‐ascertained L5 monoradiculopathy, and quantitated a global neuroforaminal and spinal stenosis score (SSS). Results: Only 9 patients (35%) had isolated L5‐root compression, 14 (54%) had multi‐root compression, and 3 (12%) had normal neuroimaging. Increasing age correlated with SSS, and the 9 patients with isolated L5‐root compression were significantly younger than patients with multi‐root involvement. Conclusions: This study underscores the role of clinical and electrodiagnostic data when interpreting lumbosacral neuroimaging, particularly in older patients. Muscle Nerve 50 : 135–137, 2014     

Memory dysfunction in panic disorder: an investigation of the role of chronic benzodiazepine use

Background: Studies of the neurocognitive effects of long‐term benzodiazepine use have been confounded by the presence of neurocognitive deficits characterizing the clinical conditions for which these medications are taken. Similarly, studies of the neurocognitive effects of anxiety disorders have been confounded by the inclusion of chronically benzodiazepine‐medicated patients. This study was designed to tease apart the potentially confounding effects of long‐term benzodiazepine use and panic disorder (PD) on memory and visuoconstructive abilities. Methods: Twenty chronically benzodiazepine‐medicated and 20 benzodiazepine‐free patients with PD with agoraphobia were compared with a group of 20 normal control participants, group‐matched for age, education, and gender on a battery of neuropsychological tests assessing short‐term, episodic long‐term, and semantic memory, as well as visuoconstructive abilities. Results: Results indicated that benzodiazepine‐free panic patients were relatively impaired in nonverbal short‐term and nonverbal episodic long‐term memory and visuoconstructive abilities, whereas verbal short‐term and verbal episodic memory and semantic memory were preserved. Only limited evidence was found for more pronounced impairments in chronically benzodiazepine‐medicated PD patients. Conclusions: This study provides evidence that patients with PD are characterized by relative impairments in nonverbal memory and visuoconstructive abilities, independent of benzodiazepine use. Nonetheless, we found evidence that chronic treatment with benzodiazepines is associated with intensification of select relative impairments in this realm. Documentation of these deficits raises questions about the broader etiology of neurocognitive impairment in PD as well as its impact on daily functioning. Depression and Anxiety, 2011. © 2011 Wiley Periodicals, Inc.     

The role of electrodiagnosis with long exercise test in mcardle disease

Introduction: In this study we evaluated the role of an electrodiagnostic provocative test (long exercise test) in McArdle disease. Methods: Twenty‐five McArdle patients and 2 control groups underwent an electrodiagnostic protocol with long exercise test (LET), consisting of recording the compound muscle action potential (CMAP) before and after 5 minutes of isometric contraction. Results: The LET disclosed a postexercise decrease in CMAP amplitude in 23 of 25 McArdle patients. The immediate and long‐lasting decrease differentiated McArdle patients from controls. Patients with a normal LET demonstrated milder symptoms and/or residual myophosphorylase activity. Discussion: The LET is a sensitive, safe, and noninvasive provocative test that may guide clinicians toward molecular analysis of the myophosphorylase gene. The abnormalities observed on LET point toward complex biochemical mechanisms determined by the absence of myophosphorylase, beyond simple glycolytic blockade (ionic pump dysfunction, sarcolemmal inexcitability). The normal LET in patients with milder symptoms indicates a relationship of the LET with clinical severity, thus identifying it as a potential outcome measure. Muscle Nerve 58 : 64–71, 2018     

Patterns of clinical and electrodiagnostic abnormalities in early amyotrophic lateral sclerosis

Introduction: The distribution of clinical and neurophysiological abnormalities in patients with early amyotrophic lateral sclerosis (ALS) was investigated in an attempt to delineate patterns of disease spread. Methods: Clinical and electrodiagnostic data were collected from 150 ALS patients and analyzed based on the clinical region of onset. Results: Asymmetry of clinical and neurophysiological abnormalities was more marked in upper limb‐onset than lower limb‐onset disease. Significant rostral–caudal gradients of clinical weakness were identified in bulbar‐ and lower limb‐onset disease. Neurophysiological evidence of the ALS “split‐hand” pattern was evident irrespective of the region of disease onset. Limbs with and without evidence of clinical weakness demonstrated similar rates of abnormality on electromyography. Conclusions: These findings suggest a pattern of disease spread in ALS. This study may serve to guide ongoing development of disease quantitation biomarkers and the targeting of future neuroprotective strategies. Muscle Nerve 50: 894–899, 2014     

Focal neurological injury caused by West Nile virus infection may occur independent of patient age and premorbid health

INTRODUCTION: Limited evidence suggests that focal neurological injury (e.g., acute flaccid paralysis) caused by infection with the West Nile virus (WNV) is more common in older patients. We re-evaluate this association in a series of patients who were infected with the WNV during the 2002 epidemic. METHODS: We performed a retrospective chart review of 34 patients who were hospitalized for treatment of serologically confirmed WNV infection. Measurements included the patient's demographic characteristics, baseline medical diagnoses, the occurrence of symptoms and exam findings, the results of various diagnostic tests, and the patient's clinical outcome. RESULTS: Patients infected with the WNV who developed focal neurological injury were found to be comparable to patients who did not develop focal neurological injury both in terms of patient age and the number of medical conditions the patient had prior to infection. This is in contrast to WNV-infected patients who developed an encephalitis-like clinical course, or who died or were institutionalized after their hospitalization; such patients tended to be older and-in cases with a poor outcome-have more medical conditions prior to WNV infection. CONCLUSIONS: In our patient group, focal neurological injury caused by WNV infection was not related to advanced patient age or to the number of medical conditions the patient had prior to infection. Our findings bring into question commonly held views about the development of focal neurological injury caused by WNV infection, and they raise concerns about the management of future WNV epidemics and the testing and use of potential antiviral treatments against this infection.     

Single‐fiber EMG and clinical correlation in Lambert‐Eaton myasthenic syndrome

Objectives: We analyzed 82 single‐fiber EMG (SFEMG) tests in the extensor digitorum communis muscle in 30 Lambert‐Eaton myasthenic syndrome (LEMS) patients to study the relationship between electrodiagnostic findings and clinical severity. Methods: The repetitive nerve stimulation test was performed in the abductor digiti quinti and flexor carpi ulnaris muscles. SFEMG was performed in the extensor digitorum communis muscle using the conventional method. Results: Fiber density was normal in all patients. Jitter was abnormal in all patients at the first evaluation regardless of clinical severity. The jitter was increasingly abnormal with worsening disease severity. Mean MCD correlated well with clinical and electrophysiological severity. In 5 potential pairs in 3 patients, MCD analysis in relation to firing rate showed improvement with increasing firing rates, which is consistent with presynaptic neuromuscular transmission disorders. Conclusions: In all LEMS studies, SFEMG was abnormal on the first evaluation. The mean MCD correlated well with clinical and electrophysiological disease severity on the repetitive nerve stimulation test. Muscle Nerve 47: 664–667, 2013     

Outcomes following surgery for peroneal intraneural ganglion cysts

Introduction: The objective of this study was to answer the typical questions from patients regarding the likely neurologic outcome and likelihood of recurrence when discussing peroneal intraneural ganglion cysts preoperatively. Methods: Retrospective analysis of all patients who underwent surgery for a peroneal intraneural ganglion cyst between January 1, 2000, and April 1, 2017, was performed. Postoperative neurologic outcomes and radiologic recurrences are reported. Results: There were 65 patients. Average clinical follow‐up was 14 months. Median dorsiflexion and eversion preoperatively were 2/5 and 4/5, respectively. Median dorsiflexion and eversion at last follow‐up postoperatively were 5/5. Radiologic recurrence occurred in 6 (9%) patients, all extraneural. Discussion: The data support excellent postoperative motor outcomes, despite frequent dense weakness of peroneal‐innervated musculature preoperatively. The surgical approach appears to eliminate risk of intraneural recurrence and minimizes risk of extraneural recurrence. Muscle Nerve 57 : 989–993, 2018     

Idiopathic phrenic neuropathies: A case series and review of the literature

Introduction: Phrenic neuropathies (PNs) are a major cause of dyspnea, orthopnea, and hypercapnic respiratory failure. The aim of the study was to obtain diagnostic findings, assess therapeutic options, and review outcomes in PN patients. Methods: From 2004 to 2013, patients with PN referred to the author's institution were studied using clinical, pulmonary function, and electrodiagnostic tests. A PubMed search of published PN reports was also done. Unilateral PN (UPN) and bilateral PN (BPN) patients were compared. Results: The analysis consisted of 10 UPN and 9 BPN patients seen by the author, plus previous reports of 18 UPN and 40 BPN patients. BPN patients were older (in the author's series) and were more often hypertensive. They reported pain less often, dyspnea and orthopnea more often, and had worse results on pulmonary function tests than UPN patients. Conclusions: UPN and BPN are probably 2 variants of the same, immune‐mediated focal neuropathy. Electrodiagnosis is a valuable confirmatory test for PN. Muscle Nerve 52 : 986–992, 2015     

Neuromuscular junction disorders mimicking myopathy

Introduction: Small‐amplitude, short‐duration motor unit action potentials are non‐specific findings seen in myopathies and neuromuscular junction (NMJ) disorders. NMJ studies (repetitive nerve stimulation and single‐fiber electromyography) can determine if such findings are related to NMJ abnormalities but are not considered routinely in atypical cases. Methods: Medical records of 338 patients with confirmed NMJ disorders were reviewed to identify cases with a clinical or electrodiagnostic impression of myopathy during initial evaluation. A history of muscle biopsy with findings that did not support a myopathic process was required for inclusion. Results: Four patients met the inclusion criteria. NMJ studies were abnormal in all cases. One patient had elevated acetylcholine receptor antibodies. Three patients were antibody negative: 2 demonstrated immunotherapy responsiveness, and 1 had a Rapsyn mutation. Conclusions: NMJ disorders may mimic myopathies, and NMJ studies should be performed to clarify so‐called “myopathic” electromyographic findings to avoid unnecessary testing and delayed diagnosis. Muscle Nerve 50 : 854–856, 2014     

Long‐term seizure outcome following epilepsy surgery in the parietal lobe: a meta‐analysis

Aim. Due to a limited number of patients with drug‐resistant parietal lobe epilepsy in surgical series, there are insufficient data about long‐term seizure outcome following surgery restricted to the parietal lobe. We performed a meta‐analysis to asses long‐term outcomes in patients with parietal lobe epilepsy who underwent surgery confined to the parietal lobe or resection with major involvement of the parietal cortex. Methods. An English language literature search for studies on parietal lobe surgery and outcome was conducted using the MEDLINE database, followed by a manual search based on specific criteria. An inverse variance random effect meta‐analysis model was used to estimate the pooled proportion of Engel Class I. Meta‐regression models were used to examine the association between outcome and potential predictors. Results. The search yielded seven retrospective studies with a total sample size of 253 patients (mean follow‐up: 104.9±74.8 months). Following surgery, Engel Class I surgical outcome was achieved in 62.4% (95% CI: 0.492–0.755). Two independent predictors were identified for positive long‐term outcome: interictal EEG localized to the parietal region (p=0.007) and the presence of tumour (p=0.022). Conclusion. Following surgery confined to the parietal lobe or resection with major involvement of the parietal cortex, the long‐term prognosis of patients with parietal lobe epilepsy is favourable.