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 infection presenting as acute flaccid paralysis in an HIV-infected patient: a case report and review of the literature

We describe a case of West Nile virus (WNV) infection in an HIV-infected patient who presented with an isolated flaccid monoparesis of the right upper extremity. To our knowledge, this is the first reported case of flaccid paralysis caused by WNV infection in an HIV-infected patient. We then review the medical literature on WNV infection occurring among patients who are infected with HIV. Unlike most of the cases reported in the literature, our patient had partial recovery of his neurologic deficits.     

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.     

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.     

Naturally acquired West Nile virus encephalomyelitis in transplant recipients: clinical, laboratory, diagnostic, and neuropathological features

BACKGROUND: In the 2003 West Nile virus (WNV) epidemic, Colorado reported more WNV cases than any other state, including an unprecedented number in organ transplant recipients. METHODS: Physicians caring for transplant recipients hospitalized with naturally acquired WNV encephalitis provided data to characterize the clinical symptoms, results of diagnostic studies, and outcomes. RESULTS: Eleven transplant recipients were identified (4 kidney, 2 stem cell, 2 liver, 1 lung, and 2 kidney/pancreas). Seven were directly admitted to 1 of the 2 hospitals in the study, and 4 were referred to 1 of these centers from regional hospitals. All but 1 patient had a prodrome typical of WNV encephalitis in nonimmunosuppressed patients. Ten patients developed meningoencephalitis, which in 3 cases was associated with acute flaccid paralysis. One patient developed acute flaccid paralysis without encephalitis. Six patients had significant movement disorders including tremor, myoclonus, or parkinsonism. All patients had cerebrospinal fluid pleocytosis and WNV-specific IgM in the cerebrospinal fluid and/or serum. Cerebrospinal fluid cytologic studies (n = 5) showed atypical lymphocytes, some resembling plasma cells; however, flow cytometry (n = 3) showed that cells were almost exclusively of T-cell (not B-cell or plasma cell) lineage. Magnetic resonance images of the brain were abnormal in 7 of 8 tested patients, and electroencephalograms were abnormal in 7 of 7, with 2 showing periodic lateralized epileptiform discharges. Nine of 11 patients survived infection, but 3 had significant residual deficits. One patient died 17 days after admission, and autopsy findings revealed severe panencephalitic changes with multifocal areas of necrosis in the cerebral deep gray nuclei, brainstem, and spinal cord as well as diffuse macrophage influx in the periventricular white matter. A second patient died of complications of WNV encephalitis 6 months after hospital admission. CONCLUSIONS: Naturally acquired WNV encephalitis in transplant recipients shows diagnostic, clinical, and laboratory features similar to those reported in nonimmunocompromised individuals, but neuroimaging, electroencephalography, and autopsy results verify that these patients develop neurological damage at the severe end of the spectrum.     

Recognition and Management of Acute Flaccid Myelitis in Children

BackgroundIn 2014-2015, several regions of the United States experienced an outbreak of acute flaccid myelitis in pediatric patients. A common, unique feature was disease localization to the gray matter of the spinal cord.MethodsWe report 11 children, ages 13 months to 14 years (median 9 years), in the Intermountain West who presented with extremity weakness (n = 10) or cranial neuropathy (n = 1) of varying severity without an apparent etiology.ResultsAll children experienced acute paralysis, and 10 had symptoms or signs that localized to the spinal cord. Maximum paralysis occurred within 4 days of onset in all patients. All had spinal gray matter lesions consistent with acute myelitis detected by magnetic resonance imaging; no single infectious cause was identified. Despite therapy with intravenous immunoglobulin, corticosteroids, or plasma exchange, nine of 10 (90%) children had motor deficits at follow-up.ConclusionsRecognition of this disorder enables clinicians to obtain appropriate imaging and laboratory testing, initiate treatment, and provide families with accurate prognostic information. In contrast to other causes of acute flaccid paralysis in childhood, most children with acute flaccid myelitis have residual neurological deficits.     

Clinical and biochemical spectrum of hypokalemic paralysis in North: East India

Background:

Acute hypokalemic paralysis, characterized by acute flaccid paralysis is primarily a calcium channelopathy, but secondary causes like renal tubular acidosis (RTA), thyrotoxic periodic paralysis (TPP), primary hyperaldosteronism, Gitelman’s syndrome are also frequent.

Objective:

To study the etiology, varied presentations, and outcome after therapy of patients with hypokalemic paralysis.

Materials And Methods:

All patients who presented with acute flaccid paralysis with hypokalemia from October 2009 to September 2011 were included in the study. A detailed physical examination and laboratory tests including serum electrolytes, serum creatine phosphokinase (CPK), urine analysis, arterial blood gas analysis, thyroid hormones estimation, and electrocardiogram were carried out. Patients were further investigated for any secondary causes and treated with potassium supplementation.

Result:

The study included 56 patients aged 15-92 years (mean 36.76 ± 13.72), including 15 female patients. Twenty-four patients had hypokalemic paralysis due to secondary cause, which included 4 with distal RTA, 4 with Gitelman syndrome, 3 with TPP, 2 each with hypothyroidism, gastroenteritis, and Liddle’s syndrome, 1 primary hyperaldosteronism, 3 with alcoholism, and 1 with dengue fever. Two female patients were antinuclear antibody-positive. Eleven patient had atypical presentation (neck muscle weakness in 4, bladder involvement in 3, 1 each with finger drop and foot drop, tetany in 1, and calf hypertrophy in 1), and 2 patient had respiratory paralysis. Five patients had positive family history of similar illness. All patients improved dramatically with potassium supplementation.

Conclusion:

A high percentage (42.9%) of secondary cause for hypokalemic paralysis warrants that the underlying cause must be adequately addressed to prevent the persistence or recurrence of paralysis.     

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.     

West Nile virus encephalomyelitis with polio-like paralysis & nigral degeneration

BACKGROUND: Patients infected with West Nile virus (WNV) may develop acute neurologic disease, which can be severe or even fatal, including WNV meningitis, encephalitis, and an irreversible acute flaccid paralysis or poliomyelitis-like syndrome. Movement disorders have also been described. REPORT: We report combined neuronal loss, gliosis, and neurofibrillary tangle formation in the substantia nigra of a 41-year-old man with a history of WNV encephalomyelitis and poliomyelitis-like paralysis. CONCLUSIONS: Clinically our patient did not display parkinsonism, however, it is interesting to speculate whether, in the absence of the residual subacute poliomyelitis-like syndrome, the neuropathologic findings could have eventually evolved clinically into WNV-associated postencephalitic parkinsonism.     

Neuropathology of the brain and spinal cord in human West Nile virus infection

OBJECTIVE: To describe the histopathology of the brain and spinal cord in human West Nile virus (WNV) infection. MATERIALS AND METHODS: Single case report, including premortem clinical and laboratory findings, and autopsy. RESULTS: An 83-year-old female presented with acute confusion, high fevers, dysarthria and generalized subjective weakness, with decreased deep tendon reflexes and weakness on physical examination. Electromyography showed evidence of a sensorimotor axonal polyneuropathy of the right-sided extremities. She became ventilator-dependent and died after a 2-week ICU stay, following withdrawal of life support. WNV infection was confirmed premortem by detection of IgM antibodies from serum and CSF and postmortem by RT-PCR from brain tissue. Examination of the brain parenchyma showed scattered microglial aggregates accompanied by perivascular chronic inflammation. The leptomeninges showed focal lymphocytic infiltrates. Examination of the spinal cord showed lymphocytic infiltrates in nerve roots and within the cord proper, with focal microglial nodules and neuronophagia in the ventral horns. Special stains were negative for a demyelinating process. General autopsy revealed only emphysema and atelectasis. CONCLUSIONS: The findings in this case suggest direct viral infection of the spinal cord and nerve roots as the mechanism of the flaccid paralysis often observed in patients infected with WNV. Findings are reviewed in comparison with other reports of neuropathologic findings in human WNV infection.     

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.     

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.     

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.     

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.     

伴感染性低血钾性麻痹的系统分析

目的 探讨感染与低血钾性麻痹之间的关系及其临床特点。方法 对本组34例及国内文献报道的115例低血钾性麻痹的病例进行感染过程。临床表现,血钾,肌酶,电生理及病毒学检测结果的系统分析。结果 发现各类报道病例间的临床表现及对本病的命名不一致,病毒感染缺乏确切依据,本病的典型表现为在感染过程中发生的四肢急性迟缓性瘫痪,伴低血钾,无神经系统其他损害的表现,预后良好,多数不再复发。结论 目前尚缺乏足够证据确定本病为一独立的疾病单元,命名以“伴感染性低血钾性麻痹”较为恰当,可能是一组有遗传易感基因,易在感染过程中发病的综合征。     

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.     

Thyrotoxic hypokalemic periodic paralysis as the presenting symptom of silent thyroiditis

Silent thyroiditis is a rare cause of thyrotoxic periodic paralysis. The objective was to present a case of silent thyroiditis presenting as periodic paralysis. A 23-year-old man presented with recurrent acute flaccid predominantly proximal weakness of all four limbs. He had a similar episode 3 weeks back. On examination he was found to have hypokalemia secondary to thyrotoxicosis. Clinically there were no features of thyrotoxicosis or thyroiditis. He was initially treated with intravenous and later oral potassium supplementation and propranolol. At 8 weeks of follow-up his thyroid profile became normal and his propranolol was stopped. He had no further recurrence of paralysis. He was diagnosed as a case silent thyroiditis presenting as thyrotoxic periodic paralysis. In cases of recurrent or acute flaccid muscle paralysis, it is important to suspect thyrotoxicosis, even if asymptomatic. Definitive treatment of thyrotoxicosis prevents recurrence.     

Etiological spectrum of hypokalemic paralysis: A retrospective analysis of 29 patients

Background:

Hypokalemic paralysis is characterized by episodes of acute muscle weakness associated with hypokalemia. In this study, we evaluated the possible etiological factors in patients of hypokalemic paralysis.

Materials and Methods:

We reviewed the records of 29 patients who were admitted with a diagnosis of hypokalemic paralysis. Modified Guillain-Barre´ Syndrome disability scale was used to grade the disability.

Results:

In this study, 15 (51.7%) patients had secondary causes of hypokalemic paralysis and 14 patients (42.3%) had idiopathic hypokalemic paralysis. Thyrotoxicosis was present in six patients (20.6%), dengue infection in four patients (13.7%), distal renal tubular acidosis in three patients (10.3%), Gitelman syndrome in one patient (3.4%), and Conn''s syndrome in one patient (3.4%). Preceding history of fever and rapid recovery was seen in dengue infection-induced hypokalemic paralysis. Approximately 62% patients had elevated serum creatinine phosphokinase. All patients had recovered completely following potassium supplementation. Patients with secondary causes were older in age, had significantly more disability, lower serum potassium levels, and took longer time to recover.

Conclusion:

In conclusion, more than half of patients had secondary causes responsible for hypokalemic paralysis. Dengue virus infection was the second leading cause of hypokalemic paralysis, after thyrotoxicosis. Presence of severe disability, severe hypokalemia, and a late disease onset suggested secondary hypokalemic paralysis.     

Unusual neurological presentations of vitamin B(12) deficiency.

Vitamin B(12) deficiency (B(12)D) has a wide variety of neurological symptoms and signs. However, cerebellar dysfunction and cranial neuropathies other than optic neuropathy have been rarely reported. Herein, we describe two cases of unusual neurological manifestations of B(12)D. One patient showed prominent hoarseness with vocal cord paralysis, myelopathy, and peripheral neuropathy. The other had gait disturbance, lateral gaze limitation and cerebellar dysfunction in addition to the typical manifestations of subacute combined degeneration. Vitamin B(12) deficiency can rarely affect cerebellum and cranial nerves other than optic nerve.     

A novel antineuronal antibody in serum and CSF of a patient with motor neuron disease.

A patient with motor neuron disease and tonic pupil who had an antinuclear antibody (Ab) in the serum and oligoclonal pattern in IgG in the CSF is described. Sera and CSF from this patient and controls (37 sera and 30 CSF) were screened for an antineuronal Ab using immunoblotting. Only the serum and CSF from this patient contained an Ab to a 70-kD protein in the human spinal cord but not in the human muscle or cerebellar cortex. This patient's serum immunohistochemically stained human and Japanese monkey anterior horn cells but not Japanese monkey dorsal root ganglion.