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.     

Asymmetric flaccid paralysis: a neuromuscular presentation of West Nile virus infection

The neuromuscular aspects of West Nile virus (WNV) infection have not been characterized in detail. We have studied a group of six patients with proven WNV infection. All cases presented with acute, severe, asymmetric, or monolimb weakness, with minimal or no sensory disturbance after a mild flu-like prodrome. Four cases also had facial weakness. Three of our cases had no encephalitic signs or symptoms despite cerebrospinal fluid pleocytosis. Electrophysiological studies showed severe denervation in paralyzed limb muscles, suggesting either motor neuron or multiple ventral nerve root damage. This localization is supported further by the finding of abnormal signal intensity confined to the anterior horns on a lumbar spine magnetic resonance imaging. Muscle biopsies from three patients showed scattered necrotic fibers, implicating mild direct or indirect muscle damage from the WNV infection. In summary, we describe a group of patients with acute segmental flaccid paralysis with minimal or no encephalitic or sensory signs. We have localized the abnormality to either the spinal motor neurons or their ventral nerve roots. It will be important for physicians to consider WNV infection in patients with acute asymmetric paralysis with or without encephalitic symptoms.     

Acute flaccid paralysis due to West nile virus infection in adults: A paradigm shift entity

Three cases of acute flaccid paralysis (AFP) with preceding fever are described. One patient had a quadriparesis with a florid meningoencephalitic picture and the other two had asymmetric flaccid paralysis with fasciculations at the onset of illness. Magnetic resonance imaging in two cases showed prominent hyperintensitities in the spinal cord and brainstem with prominent involvement of the grey horn (polio-myelitis). Cerebrospinal fluid (CSF) polymerase chain reaction was positive for West Nile virus (WNV) in the index patient. All three cases had a positive WNV immunoglobulin M antibody in serum/CSF and significantly high titer of WNV neutralizing antibody in serum, clearly distinguishing the infection from other Flaviviridae such as Japanese encephalitis. WNV has been recognized in India for many decades; however, AFP has not been adequately described. WNV is a flavivirus that is spread by Culex mosquitoes while they take blood meals from humans and lineage 1 is capable of causing a devastating neuro-invasive disease with fatal consequences or severe morbidity. We describe the first three laboratory confirmed cases of WNV induced AFP from Kerala and briefly enumerate the salient features of this emerging threat.     

Long‐term neuromuscular outcomes of west nile virus infection: A clinical and electromyographic evaluation of patients with a history of infection

Introduction: Neuromuscular clinical manifestations during acute West Nile virus (WNV) infection are well documented; however, long‐term neurologic outcomes still require investigation. Methods: We conducted a long‐term follow‐up study in patients with history of WNV infection. Of the 117 patients who participated in neurologic and neurocognitive evaluations, 30 were referred for neuromuscular and electrodiagnostic evaluation based on abnormal findings. Results: We found that 33% of these patients (10 of 30) showed abnormalities on nerve conduction and/or needle electromyography due to primary or secondary outcomes of WNV infection. Most common electrodiagnostic findings and causes of long‐term disability were related to anterior horn cell poliomyelitis (WNV poliomyelitis). Electrical data on these patient populations were similar to those observed in chronic poliomyelitis. Discussion: With more than 16,000 cases of WNV neuroinvasive disease reported across the USA since 1999, understanding clinical outcomes from infection will provide a resource for physicians managing long‐term care of these patients. Muscle Nerve 57 : 77–82, 2018     

Nonpoliovirus poliomyelitis simulating Guillain-Barré syndrome

BACKGROUND: Paralytic poliomyelitis due to the wild-type poliovirus has been eradicated in the United States because of effective immunization programs. In the postvaccination era, most cases are caused by other RNA viruses, such as coxsackievirus or echovirus. The condition usually begins with a fever and upper respiratory tract or gastrointestinal tract symptoms that progress to a "paralytic" phase characterized by limb weakness, areflexia, and, occasionally, respiratory failure that superficially resemble Guillain-Barré syndrome. OBJECTIVE: To describe 2 patients with nonpoliovirus poliomyelitis and highlight the findings on magnetic resonance imaging of the spinal cord to distinguish these cases from variants of Guillain-Barré syndrome. DESIGN AND SETTING: Case series from an academic medical center. PATIENTS: Following a viral illness, the patients, aged 35 and 50 years, had painless, progressive, asymmetrical weakness in the arms followed by respiratory failure in one patient, and generalized limb weakness in the other patient, reaching a nadir in 1 week. Both patients had fevers but no signs of meningitis at onset. Tendon reflexes were absent or reduced in affected regions. The cerebrospinal fluid findings were as follows: mononuclear leukocyte counts of 100 000 cells/mm(3) and 700 000 cells/mm(3), respectively, and the protein level was above 10 g/dL in both patients. Compound muscle action potential amplitudes were reduced in some nerves with active denervation in clinically affected muscles, and F-responses were absent but there were no other demyelinating features. Magnetic resonance imaging showed discrete T2-weighted signal changes of the ventral horns of the spinal cord, and one had elevated coxsackievirus titers in the serum. There was little recovery and significant atrophy in weak muscles after 3 years. CONCLUSIONS: The poliomyelitis syndrome still occurs in adults in developed countries. It has superficial similarities to a motor axonal variant of Guillain-Barré syndrome but can be distinguished by clinical, cerebrospinal fluid, and, perhaps specifically, magnetic resonance imaging characteristics.     

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.     

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     

Clinical spectrum of muscle weakness in human West Nile virus infection

Poliomyelitis has recently been identified as a cause of muscle weakness in patients with West Nile virus (WNV) infection. However, the clinical spectrum of WNV-associated weakness has not been described. We reviewed data on 13 patients with WNV infection. Patients with muscle weakness were classified into one of three distinct groups based on clinical features. Group 1 comprised five patients who developed acute flaccid paralysis, four with meningoencephalitis and one without fever or other signs of infection. Paralysis was asymmetric, and involved from one to four limbs in individual patients. Electrodiagnostic studies confirmed involvement of anterior horn cells or motor axons. Group 2 involved two patients without meningoencephalitis who developed severe but reversible muscle weakness that recovered completely within weeks. Muscle weakness involved both lower limbs in one patient and one upper limb in the other. Group 3 consisted of two patients who experienced subjective weakness and disabling fatigue, but had no objective muscle weakness on examination. In addition to the three distinct groups, two other patients developed exaggerated weakness in the distribution of preexisting lower motor neuron dysfunction. We conclude that the clinical spectrum of WNV-associated muscle weakness ranges from acute flaccid paralysis, with or without fever or meningoencephalitis, to disabling fatigue. Also, preexisting dysfunction may predispose anterior horn cells to additional injury from WNV. Awareness of this spectrum will help to avoid erroneous diagnoses and inappropriate treatment.     

West Nile virus neuroinvasive disease

Since 1999, there have been nearly 20,000 cases of confirmed symptomatic West Nile virus (WNV) infection in the United States, and it is likely that more than 1 million people have been infected by the virus. WNV is now the most common cause of epidemic viral encephalitis in the United States, and it will likely remain an important cause of neurological disease for the foreseeable future. Clinical syndromes produced by WNV infection include asymptomatic infection, West Nile Fever, and West Nile neuroinvasive disease (WNND). WNND includes syndromes of meningitis, encephalitis, and acute flaccid paralysis/poliomyelitis. The clinical, laboratory, and diagnostic features of these syndromes are reviewed here. Many patients with WNND have normal neuroimaging studies, but abnormalities may be present in areas including the basal ganglia, thalamus, cerebellum, and brainstem. Cerebrospinal fluid invariably shows a pleocytosis, with a predominance of neutrophils in up to half the patients. Diagnosis of WNND depends predominantly on demonstration of WNV-specific IgM antibodies in cerebrospinal fluid. Recent studies suggest that some WNV-infected patients have persistent WNV IgM serum and/or cerebrospinal fluid antibody responses, and this may require revision of current serodiagnostic criteria. Although there is no proven therapy for WNND, several vaccines and antiviral therapy with antibodies, antisense oligonucleotides, and interferon preparations are currently undergoing human clinical trials. Recovery from neurological sequelae of WNV infection including cognitive deficits and weakness may be prolonged and incomplete.     

AAEM case report #23: acute paralytic poliomyelitis.

A 56-year-old man with acute paralytic poliomyelitis is described. The illness started with fever and diarrhea after an overseas trip, and an enterovirus other than poliovirus was isolated from the patient's stool. The onset of weakness was rapid and asymmetric, with primary involvement of the lower extremities. Nerve conduction studies revealed low amplitude motor responses after the first week, with normal results for sensory studies. Serial electromyographic studies were performed, documenting acute denervation followed later by reinnervation in the distribution of multiple segments. The clinical and electrodiagnostic features of acute poliomyelitis are reviewed.     

Unusual Case of West Nile Virus Flaccid Paralysis in a 10-Year-Old Child

West Nile virus infection is asymptomatic in most cases. West Nile virus neuroinvasive disease includes encephalitis, meningitis, and/or acute flaccid paralysis. In children, acute flaccid paralysis as the solo presentation of West Nile virus disease is rare. It develops abruptly and progresses rapidly early in the disease course. We report on a 10-year-old child who presented with a slowly progressive left leg flaccid paralysis over 4 weeks. He tested positive for West Nile virus in both blood and cerebrospinal fluid. Spinal MRI showed enhancement of the ventral nerve roots. This was also supported by electrophysiological studies. One week after the plateauing of his left leg paralysis, he was readmitted to the hospital with left hand weakness. Complete recovery of his recurrent weakness was observed after prompt 5-day course of intravenous immunoglobulin G therapy. However, no improvement was noticed in the left foot drop. To our knowledge, this is the first case report of West Nile virus disease in children presented with a slowly progressive flaccid paralysis, and a recurrent weakness recovered after intravenous immunoglobulin G administration.     

Neuralgic amyotrophy and infectious mononucleosis: a case report

A 27 year old man developed neuralgic amyotrophy of the right upper limb 5 weeks after an acute febrile illness which was proven serologically to be caused by Ebstein-Barr virus. The weakness developed in a limb that had been used to perform heavy manual labour. A parallel with a similar phenomenon described in association with paralytic poliomyelitis is noted.-     

Acute flaccid myelitis: A clinical review of US cases 2012–2015

This review highlights clinical features of the increasing cases of acute flaccid paralysis associated with anterior myelitis noted in the United States from 2012 to 2015. Acute flaccid myelitis refers to acute flaccid limb weakness with spinal cord gray matter lesions on imaging or evidence of spinal cord motor neuron injury on electrodiagnostic testing. Although some individuals demonstrated improvement in motor weakness and functional deficits, most have residual weakness a year or more after onset. Epidemiological evidence and biological plausibility support an association between enterovirus D68 and the recent increase in acute flaccid myelitis cases in the United States. Ann Neurol 2016;80:326–338     

Approach to neuromuscular disorders in the intensive care unit

Neuromuscular disorders increasingly are recognized as a complication in patients in the intensive care unit (ICU) and represent a common cause of prolonged ventilator dependency. The distinct syndromes of critical illness myopathy, prolonged neuromuscular blockade, and critical illness polyneuropathy (CIP) may arise as a consequence of sepsis, multi-organ failure, and exposure to various medications—notably, intravenous corticosteroids and neuromuscular blocking agents—but the pathophysiology of these disorders remains poorly understood. More than one syndrome may occur simultaneously, and the distinctions may be difficult in a particular patient, but a specific diagnosis usually can be established after careful clinical, electrodiagnostic, and, when necessary, histological evaluation. For example, asthmatics requiring treatment with corticosteroids and neuromuscular blocking agents may develop an acute myopathy characterized by generalized weakness, preserved eye movements, elevated creatine kinase levels, and myopathic motor units on electromyography (EMG). Muscle biopsy demonstrates distinctive features of thick (myosin) filament loss on ultrastructural studies. Conversely, those with a prolonged ICU course that is complicated by episodes of sepsis with failure to wean from the ventilator, distal or generalized flaccid limb weakness, and areflexia probably have CIP. EMG in these patients demonstrates reduced or absent motor and sensory potentials with neurogenic motor units. Prolonged neuromuscular blockade most commonly occurs in patients with renal failure who have received prolonged infusions of neuromuscular blockers. There is severe flaccid, areflexic paralysis with normal sensation, facial weakness, and ophthalmoparesis that persists for days or weeks after the neuromuscular blockers have been discontinued. Repetitive nerve stimulation shows a decrement of the compound muscle action potential and, in most cases, establishes a disorder of neuromuscular transmission. With the recent epidemic of West Nile virus infection, a clinical syndrome of acute flaccid paralysis with several features indistinguishable from poliomyelitis has emerged. This article critically examines the clinical, electrophysiological, and pathological features of these and other acute neuromuscular syndromes that arise in the context of ICU care and summarizes the current understanding of the pathophysiology and treatment of these disorders.     

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     

West Nile virus—induced acute flaccid paralysis is prevented by monoclonal antibody treatment when administered after infection of spinal cord neurons

Acute flaccid polio-like paralysis occurs during natural West Nile virus (WNV) infection in a subset of cases in animals and humans. To evaluate the pathology and the possibility for therapeutic intervention, the authors developed a model of acute flaccid paralysis by injecting WNV directly into the sciatic nerve or spinal cord of hamsters. By directly injecting selected sites of the nervous system with WNV, the authors mapped the lesions responsible for hind limb paralysis to the lumbar spinal cord. Immunohistochemical analysis of spinal cord sections from paralyzed hamsters revealed that WNV-infected neurons localized primarily to the ventral motor horn of the gray matter, consistent with the polio-like clinical presentation. Neuronal apoptosis and diminished cell function were identified by TUNEL (terminal deoxynucleotidyl transferase—mediated BrdUTP nick end labeling) and choline acetyltransferase staining, respectively. Administration of hE16, a potently neutralizing humanized anti-WNV monoclonal antibody, 2 to 3 days after direct WNV infection of the spinal cord, significantly reduced paralysis and mortality. Additionally, a single injection of hE16 as late as 5 days after WNV inoculation of the sciatic nerve also prevented paralysis. Overall, these experiments establish that WNV-induced acute flaccid paralysis in hamsters is due to neuronal infection and injury in the lumbar spinal cord and that treatment with a therapeutic antibody prevents paralysis when administered after WNV infection of spinal cord neurons.     

Post-polio syndrome. A case report

Certain acute anterior poliomyelitis survivors express complaints of abnormal fatigue, weakness and muscular atrophy many years after acute onset. These are basic clinical symptoms of so-called post-polio syndrome (PPS). PPS is characterized by a relatively slow, but progressive pathological muscular process, in some cases leading to functional impairment of daily living and professional activity. Breathing, speaking and swallowing impairment are common but not severe medical problems of post-polio patients. Diagnosis is usually based on a typical medical history, electromyographic investigation and exclusion of other diseases presenting similar features. We report a case of PPS in a 49-year-old woman diagnosed in the Neurological Department in Zabrze. Thirty six years after acute anterior poliomyelitis with partial recovery, new symptoms of fatigue, muscular atrophy, exertional dyspnea, walking impairment and joint pain developed. Electromyography revealed features of coexisting spinal denervation and reinnervation in tested muscles. The differential diagnosis excluded other neuromuscular diseases. The patient fulfilled clinical and electromyographic criteria of PPS.     

Neuromuscular disease and respiratory failure

Neurologists should be able to anticipate and recognise the onset of respiratory failure in patients with neuromuscular disorders. Symptoms will differ depending on the speed of onset of the respiratory muscle weakness. Careful monitoring of respiratory function is particularly important in acute disorders such as Guillain-Barré syndrome. Patients with an unrecognised neuromuscular disorder may occasionally present with respiratory failure. Important investigations include vital capacity, mouth pressures, arterial blood gases, chest x ray and sometimes overnight respiratory monitoring. Patients with Guillain-Barré and other acute conditions may require short-term ventilatory support in the intensive care unit. Patients with some chronic disorders, such as motor neuron disease and Duchenne dystrophy, can be successfully treated with non-invasive ventilation, usually in collaboration with a respiratory physician. New-onset weakness of limb and respiratory muscles in the intensive care unit is usually due to critical illness myopathy or critical illness polyneuropathy, and treatment is supportive.     

Rare ocular manifestation in a case of West Nile virus meningoencephalitis

West Nile Virus (WNV) is an arthropod-borne flavivirus, which causes flu-like illness and is sporadically associated with encephalitis. Transmission to humans occurs following a bite from an infected mosquito, which acquires the virus after feeding on dead birds. WNV meningoencephalitis is a rare infection with a neuroinvasive disease occurring in less than 1% of the cases, with varied presentations including aseptic meningitis, meningoencephalitis, and acute flaccid paralysis. Chorioretinitis is the most common eye finding in this infection, while other ocular manifestations have been rarely reported in the literature. We present the first case report of WNV meningoencephalitis, with rare ocular manifestations of acute hemorrhagic conjunctivitis, bilateral subconjunctival hemorrhages, and nystagmus. The rare ocular findings of acute hemorrhagic conjunctivitis, bilateral subconjunctival hemorrhages, and nystagmus diagnosed in our case can guide clinicians toward early diagnosis of WNV meningoencephalitis, while serologic testing is still pending.