The effect of botulinum toxin application on latissimus dorsi and teres major muscles in patients with brachial plexus birth palsy: An electron microscopic and clinical study.

BACKGROUND: In brachial plexus birth palsy (BPBP), botulinum toxin may be utilized to prevent glenohumeral dysplasia and to maintain the stable growth of the glenohumeral joint. Repeated injections may cause muscular atrophy and their functional effects are uncertain. The aim of this study was to compare the microstructure and the function of the muscles that received two injections before transfer with the muscles that were not injected. METHODS: BPBP patients that were operated between January 2013 and December 2015 were included in the study. Latissimus dorsi and teres major muscles were transferred to humerus in standard fashion. Patients were divided in two groups according to bo-tulinum toxin status. Group 1 was toxin negative whereas Group 2 was toxin positive. For each patient, mean latissimus dorsi myocyte thickness (LDMT) was measured with electron microscopy and pre-operative and post-operative active shoulder abduction, flexion, external and internal rotation, and Mallet scores were evaluated with goniometry. RESULTS: Fourteen patients (seven patients per group) were evaluated. Five patients were female whereas nine were male. Mean LDMT was not affected significantly (p>0.05). The operation improved shoulder abduction, flexion, and external rotation significantly (p<0.05), independent of the toxin status. The internal rotation decreased significantly only in Group 2 (p<0.05). The Mallet score increased in both groups, but it was not significant (p>0.05), independent of the toxin status. CONCLUSION: Botulinum toxin that was applied twice prevented glenohumeral dysplasia and it did not cause permanent latissimus dorsi muscle atropy and function loss in late period. It augmented upper extremity functions by alleviating internal rotation contracture.

Oral Methadone for Patients With Neuropathic Pain Due to Neoplastic Brachial Plexopathy.

Background: The brachial plexus nerves originate from the cervical (C5-C8) and first thoracic (T1) spinal nerves, and innervate muscles and skin of the chest, shoulder, arm and hand. Brachial plexus injuries can occur as a result of shoulder trauma and inflammation. Malignant tumors can also cause neoplastic brachial plexopathy (NBP), and refractory neuropathic pain is the most common symptom of NBP. Methadone is a synthetic opioid with high efficacy as an opioid-receptor agonist, and its inhibitory effects on N-methyl-D-aspartate (NMDA) may play a role in pain relief. However, there is a need to examine if oral methadone exhibits safety and efficacy against neuropathic pain due to NBP. Case Presentations: NBP was diagnosed in 3 cases without brain or cervical spine metastasis. The clinical features of these patients were analyzed retrospectively. None of the cases had an indication for surgery because of advanced cancer and all had received radiation therapy that had an insufficient effect, prior to methadone treatment. All 3 patients had nociceptive and neuropathic pain. Methadone for refractory pain was initiated using the stop-and-go method. NRS pain scores decreased in all cases and there were no severe side effects. Discussion: For the purpose of pain relief, patients with NBP may receive surgery, radiation therapy and nerve block, but these are not always effective. Methadone was recently shown to be superior to fentanyl in treating neuropathic pain in patients with head-and-neck cancer in a RCT, and our findings suggest that methadone may also be effective for patients with NBP. Conclusion: More studies are necessary, but results in 3 cases suggest that oral methadone may be a safe analgesic agent for patients with neuropathic pain due to NBP.

Severe brachial plexopathy secondary to shingles (herpes zoster).

Varicella zoster reactivation ("shingles" or "herpes zoster") usually presents as a self-limiting, unilateral, dermatomal vesicular rash in older adults. We present the case of a 73 year-old woman with unilateral brachial plexopathy, an unusual but debilitating complication of shingles. Despite treatment with intravenous acyclovir and immunoglobulin she had a marked residual motor paresis that required an upper limb rehabilitation program after discharge.

Local Riluzole Release from a Thermosensitive Hydrogel Rescues Injured Motoneurons through Nerve Root Stumps in a Brachial Plexus Injury Rat Model.

The C5-C6 nerve roots are usually spared from avulsion after brachial plexus injury (BPI) and can thus be used as donors for nerve repair. A BPI rat model with C5-C6 nerve root stumps has been established in our previous work. The aim of this study was to test whether riluzole loaded into a thermosensitive hydrogel could applied locally in the nerve root stumps of this BPI rat model, thus increasing the reparative effect of the nerve root stumps. Nile red (a hydrophobic dye) was used as a substitute for riluzole since riluzole itself does not emit light. Nile red, loaded into a thermosensitive hydrogel, was added to the nerve root stumps of the BPI rat model. Additionally, eighteen rats, with operation on right brachial plexus, were evenly divided into three groups: control (Con), thermosensitive hydrogel (Gel) and thermosensitive hydrogel loaded with riluzole (Gel + Ri) groups. Direct nerve repair was performed after local riluzole release for two weeks. Functional and electrophysiological evaluations and histological assessments were used to evaluate the reparative effect 8 weeks after nerve repair. Nile red was slowly released from the thermosensitive hydrogel and retrograde transport through the nerve root stumps to the motoneurons, according to immunofluorescence. Discernible functional recovery began earlier in the Gel + Ri group. The compound muscle action potential, ChAT-expressing motoneurons, positivity for neurofilaments and S100, diameter of regenerating axons, myelin sheath thickness and density of myelinated fibers were markedly increased in the Gel + Ri group compared with the Con and Gel groups. Our results indicate that the local administration of riluzole could undergo retrograde transportation through C5-C6 nerve root stumps, thereby promoting neuroprotection and increasing nerve regeneration.

Outcomes of Botulinum Toxin Injection for Shoulder Internal Rotation Contractures in Infants with Brachial Plexus Birth Injury.

PURPOSE: Shoulder internal rotation contractures (IRC) are common sequela of brachial plexus birth injuries (BPBI). Botulinum toxin A (BTX-A) injection into targeted muscles has been described to facilitate functional improvement at the shoulder joint and prevent glenohumeral dysplasia. The purpose of this study was to assess the outcomes of BTX-A injections on shoulder IRC in children with BPBI. METHODS: We conducted a retrospective analysis of 47 children with shoulder IRC due to BPBI, who were treated with BTX-A. Shoulder passive external rotation in adduction and Active Movement Scale external rotation scores were recorded before and after BTX-A injection. We also recorded the number of children who underwent secondary surgical balancing procedures to improve shoulder motion after BTX-A injection. RESULTS: Mean age at the time of injection was 12 months (range, 5-23 months). Subjects demonstrated a significant increase in passive external rotation of 46° (range, 10° to 90) at 4 months; an average improvement of 18° (range, -30° to 80°) persisted at 11 months after injection. A total of 28 patients (60%) underwent subsequent external rotation tendon transfer. At 5-year follow-up, 7 patients (15%) had adequate functional shoulder range of motion and did not undergo external rotation tendon transfer. CONCLUSIONS: Botulinum toxin A injections result in improvement in IRC due to BPBI, which is sustained beyond the expected half-life of 3 months. As many as 15% of patients who have this treatment avoid external rotation tendon transfer. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

Management of neuropathic pain following traumatic brachial plexus injury with neurolysis and oral gabapentin: A case report.

Neuropathic pain responds poorly to common analgesics that effectively control nociceptive pain because its pathophysiology is different and it is usually associated with co-morbidities such as sleep disturbance, depression and anxiety. Patients with this chronic pain are sometimes left with neurolysis as the last resort. A 65-year-old male multiply-injured retiree presented with disabling pain following traumatic brachial plexus injury sustained from road traffic accident 5 years earlier. Other injuries resolved with therapy except the chronic severe burning and electrifying pain (VAS score 9) in the paralyzed left upper limb associated with allodynia and insomnia which was unresponsive to conventional analgesics. PainDETECT score was 29. A test supraclavicular block with 0.25% Bupivacaine was done, followed by chemical neurolysis one month later. He was placed on oral Gabapentin. The pain score a week post injection was 3 and has remained same 18 months post injection. Patient's level of satisfaction on 5 point Likert scale was 5. Chronic neuropathic pain following traumatic brachial plexus injury could be successfully managed by chemical neurolysis and oral gabapentin.

Ultrasound-guided peri-brachial plexus polydeoxyribonucleotide injection for a patient with postherpetic brachial plexopathy: A case report.

RATIONALE: Although most complications of herpes zoster (HZ) are associated with the spread of varicella-zoster virus from the initially involved sensory ganglion, motor nerve impairment, such as limb weakness, is a rare but severe complication that is difficult to treat. PATIENT CONCERN: A 73-year-old female presented with sudden left upper limb pain and weakness after HZ. DIAGNOSIS: Brachial plexopathy following HZ (postherpetic brachial plexopathy). INTERVENTION: Despite alleviation of the vesicles with antiviral treatments, the left upper limb weakness and neuropathic pain did not improve. After obtaining patient's consent, ultrasound-guided polydeoxyribonucleotide (PDRN) injection was performed around the left brachial plexus. OUTCOMES: The patient showed marked improvement in left arm pain from numerical rating scale (NRS) 9 to 4, 1 day after PDRN injection. Subsequently, the pain improved to NRS 3, and motor weakness improved to Medical Research Council grade 2 to 4. LESSONS: PDRN can be considered a viable substitute for corticosteroid injection in treatment of motor weakness and neuropathic pain after HZ.

Man-In-The-Barrel Syndrome: Acute bilateral brachial plexopathy after recurrent microtrauma.

The presence of brachial diplegia despite the normal muscular strength of the lower extremities is called the man-in-the-barrel syndrome (MIBS). Although this rare syndrome often occurs due to the bilateral supratentorial brain lesions, it may also rarely occur as a result of infratentorial causes. In this report, we describe a case presenting with MIBS of which etiological underlying cause was bilateral brachial plexopathy developed secondarily to recurrent microtrauma. A 51-year-old male patient presented to our clinic with complaints of pain and weakness on both arms. After electrodiagnostic examination, bilateral brachial plexopathy was identified. The findings of the patient improved following methylprednisolone therapy. It is very important to determine the treatable causes of this syndrome at an early stage.

Administration of Curcumin Alleviates Neuropathic Pain in a Rat Model of Brachial Plexus Avulsion.

BACKGROUND/AIMS: Brachial plexus avulsion (BPA) generally causes a chronic persistent pain that lacks efficacious treatment. Curcumin has been found to possess anti-inflammatory abilities. However, little is known about the mechanisms and effects of curcumin in an animal model of BPA. METHODS: Mechanical withdrawal thresholds (MWT) were examined by von Frey filaments. Cold allodynia was tested by the acetone spray test. The levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in rat spinal cords were analyzed by the enzyme-linked immunosorbent assay, and the expression levels of c-Fos and nerve growth factor (NGF) were measured by Western blot. The expression level of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence and Western blot. RESULTS: After curcumin treatment, the MWT showed a significant increase when compared to the BPA group on both hind paws. A remarkable decrease of paw-withdrawal response frequency was observed compared with the BPA group. In addition, curcumin treatment significantly decreased the levels of TNF-α and IL-6 in rat spinal cords that were exceedingly upregulated in the BPA group. The protein levels of c-Fos and NGF were decreased by treatment with curcumin compared with the corresponding protein levels in the BPA group. Besides, curcumin reduced the number of GFAP positive cells and GFAP expression. CONCLUSIONS: Our findings suggest that curcumin significantly extenuates the BPA-induced pain and inflammation by reducing the expression level of proinflammatory cytokines and pain-associated proteins and inhibiting the activity of astrocytes.

The Use of Botulinum Toxin Injection for Brachial Plexus Birth Injuries: A Systematic Review of the Literature.

BACKGROUND: Most brachial plexus birth injuries (BPBIs) are caused by traction on the brachial plexus during a difficult delivery. Fortunately, the possibility of complete recovery from such an incident is relatively high, with only 10% to 30% of patients having prolonged and persistent disability. These patients have muscle imbalances and co-contractions typically localized around the shoulder and elbow. These imbalances and co-contractures cause abnormal motor performances and bone/joint deformities. Typically, physical/occupational therapies are the conventional therapeutic modalities but are often times inadequate. Botulinum toxin A (BTX-A) injections into targeted muscles have been used to combat the muscular imbalances and co-contractions. METHODS: With compliance to PRISMA guidelines, a systematic review was performed to identify studies published between 2000 and 2017 that used BTX-A to treat neonatal brachial plexus palsies. RESULTS: Ten studies were included, involving 325 patients. Three groups of indications for the use of BTX-A were identified: (1) internal rotation/adduction contracture of the shoulder; (2) elbow flexion lag/elbow extension lag; and (3) forearm pronation contracture. CONCLUSIONS: The included studies show an overall beneficial effect of BTX-A in treating co-contractures seen in patients with BPBI. Specifically, BTX-A is shown to reduce internal rotation/adduction contractures of the shoulder, elbow flexion/extension contractures, and forearm pronation contractures. These beneficial effects are blunted when used in older patients. Nevertheless, BTX-A is a useful treatment for BPBIs with a relatively low-risk profile.

Utility of ultrasound-guided injection of botulinum toxin type A for muscle imbalance in children with obstetric brachial plexus palsy: Description of the procedure and action protocol. / Utilidad del tratamiento con infiltraciones ecoguiadas de toxina botulínica A en el desequilibrio muscular de niños con parálisis obstétrica del plexo braquial. Descripción del procedimiento y protocolo de actuación.

INTRODUCTION: Obstetric brachial plexus palsy (OBPP) usually has a favourable prognosis. However, nearly one third of all severe cases have permanent sequelae causing a high level of disability. In this study, we explore the effectiveness of ultrasound-guided injection of botulinum toxin A (BoNT-A) and describe the procedure. PATIENTS AND METHODS: We designed a prospective, descriptive study including patients with moderate to severe OBPP who were treated between January 2010 and December 2014. We gathered demographic data, type of OBPP, and progression. Treatment effectiveness was assessed with the Active Movement Scale (AMS), the Mallet classification, and video recordings. RESULTS: We gathered a total of 14 133 newborns, 15 of whom had OBPP (1.6 per 1000 live births). Forty percent of the cases had severe OBPP (0.4/1000), a dystocic delivery, and APGAR scores < 5; mean weight was 4038g. Mean age at treatment onset was 11.5 months. The muscles most frequently receiving BoNT-A injections were the pronator teres, subscapularis, teres major, latissimus dorsi, and pectoralis major. All the patients who completed the follow-up period (83%) experienced progressive improvements: up to 3 points on the AMS and a mean score of 19.5 points out of 25 on the Mallet classification at 2 years. Treatment improved muscle function and abnormal posture in all cases. Surgery was avoided in 3 patients and delayed in one. Adverse events were mild and self-limited. CONCLUSIONS: Due to its safety and effectiveness, BoNT-A may be used off-label as an adjuvant to physical therapy and/or surgery in moderate to severe OBPP. Ultrasound may increase effectiveness and reduce adverse effects.

Fisher-Pharyngeal-Cervical-Brachial Overlap Syndrome With Novel Ganglioside Antibodies.

Several variants of Guillain-Barré syndrome have been described. The Fisher syndrome (FS) presents with ataxia, areflexia, and ophthalmoparesis. The pharyngeal-cervical-brachial (PCB) variant presents with bulbar weakness, along with arm and neck weakness. The 2 variant syndromes can overlap. Both the isolated and overlap syndromes respond to immunomodulatory treatment, thus are important to recognize clinically. Ganglioside antibodies are detectable in the variant syndromes and may aid in their diagnosis. The FS typically is associated with anti-GQ1b antibodies, and PCB is typically associated with anti-GT1a antibodies, whereas the overlap syndrome may have both ganglioside antibody subtypes. We present a case of overlap FS-PCB syndrome with a novel ganglioside antibody profile of GM1 and GD1b antibodies, which typically are associated with other variant syndromes. This case suggests the need for all ganglioside antibodies to be tested in suspected variant Guillain-Barré syndromes. The antibodies may prove especially useful in cases in which the clinical diagnosis is ambiguous.

Neurolymphomatosis of the Brachial Plexus and its Branches: Case Series and Literature Review.

BACKGROUND: Neurolymphomatosis is a process of neoplastic endoneurial invasion, most strongly associated with non-Hodgkin's lymphoma. It must be distinguished from paraneoplastic, metabolic, nutritional and treatment-related causes of neuropathy that are common in this patient population. METHODS: This brief case series illustrates the protean manifestations of neurolymphomatosis of the brachial plexus, ranging from focal distal mononeuropathy to multifocal brachial plexopathy, either as the index manifestation of lymphoma or as a complication of relapsing disease. RESULTS: Prominent asymmetry, pain and nodular involvement on neuroimaging may help distinguish neurolymphomatosis from paraneoplastic immune demyelinating radiculoneuropathy. MR neurography criteria for the diagnosis of neurolymphomatosis include hyperintensity on T2 and STIR sequences, focal and diffuse nerve enlargement with fascicular disorganization and gadolinium enhancement. No specific anatomical distribution within the brachial plexus has, however, been found to be characteristic. Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is the imaging modality with the highest sensitivity for detection of nodal or extranodal spread in lymphoma. CONCLUSIONS: Brachial plexus neuropathy in neurolymphomatosis is highly protean in its distribution, semiology and relation to lymphoma staging. Dedicated MRI and PET-CT imaging are leading diagnostic modalities.

External Rotation Predicts Outcomes After Closed Glenohumeral Joint Reduction With Botulinum Toxin Type A in Brachial Plexus Birth Palsy.

BACKGROUND: Few studies have investigated outcomes after adjunct botulinum toxin type A (BTX-A) injections into the shoulder internal rotator muscles during shoulder closed reduction and spica cast immobilization in children with brachial plexus birth palsy. The purpose of this study was to report success rates after treatment and identify pretreatment predictors of success. METHODS: Children with brachial plexus birth palsy who underwent closed glenohumeral joint reduction with BTX-A and casting were included. Minimum follow-up was 1 year. Included patients did not receive concomitant shoulder surgery nor undergo microsurgery within 8 months. Records were reviewed for severity of palsy, age, physical examination scores, passive external rotation (PER), and subsequent orthopaedic procedures (repeat injections, repeat reduction, shoulder tendon transfers, and humeral osteotomy). Treatment success was defined in 3 separate ways: no subsequent surgical reduction, no subsequent closed or surgical reduction, and no subsequent procedure plus adequate external rotation. RESULTS: Forty-nine patients were included. Average age at time of treatment was 11.5 months. Average follow-up was 21.1 months (range, 1 to 9 y). Thirty-two patients (65%) required repeat reduction (closed or surgical). Only 16% of all patients obtained adequate active external rotation without any subsequent procedure. Increased PER (average 41±14 degrees, odds ratio=1.21, P=0.01) and Active Movement Scale external rotation (average 1.3, odds ratio=2.36, P=0.02) predicted optimal treatment success. Limited pretreatment PER (average -1±17 degrees) was associated with treatment failure. Using the optimal definition for success, all patients with pretreatment PER>30 degrees qualified as successes and all patients with PER<15 degrees were treatment failures. CONCLUSIONS: Pretreatment PER>30 degrees can help identify which patients are most likely to experience successful outcomes after shoulder closed reduction with BTX-A and cast immobilization. However, a large proportion of these patients will still have mild shoulder subluxation or external rotation deficits warranting subsequent intervention. LEVEL OF EVIDENCE: Level IV-therapeutic.

Unilateral brachial plexopathy, a rare complication of Mycoplasma pneumoniae infection.

Few reports in the literature describe isolated peripheral neuropathies in relation to Mycoplasma pneumoniae infection without concurrent damage to the central nervous system. To our knowledge only a single case of mononeuritis multiplex with brachial plexus neuropathy coincident with M. pneumoniae has been documented until now. Here we present the first clinical case of lobar M. pneumoniae pneumonia in a 19-year-old female patient, where coincident neurological complications manifested as unilateral brachial plexus neuropathy, affecting axillar and suprascapular nerves. Isolated M. pneumoniae from sputum belonged to P1 type 2 and to MLVA type 3-6-6-2. No mutation associated with macrolide resistance in domain V of the 23S rRNA gene was detected. Serological testing of a GM1 antibody showed positive results, which might support the role of immunologic mechanisms in the pathogenesis of peripheral neuropathies related to M. pneumoniae infection.

Early Botulinum Toxin Injections in Infants With Musculoskeletal Disorders: A Systematic Review of Safety and Effectiveness.

OBJECTIVE: To report current evidence regarding the safety of intramuscular botulinum toxin injection (BTI) in children with orthopedic- and neurologic-related musculoskeletal disorders >2 years of age. DATA SOURCES: PubMed, Cochrane Library, and ScienceDirect, Google Scholar, and Web of Science. STUDY SELECTION: Two reviewers independently selected studies based on predetermined inclusion criteria. DATA EXTRACTION: Data relating to the aim were extracted. Methodologic quality was graded independently by 2 reviewers using the Physiotherapy Evidence Database scale for randomized controlled trials (RCTs) and the Downs and Black evaluation tool for non-RCTs. Level of evidence was determined using the modified Sackett scale. DATA SYNTHESIS: Data of 473 infants were analyzed. Fifty-five infants had cerebral palsy, 112 had obstetric brachial plexus palsy, 257 had clubfoot, and 44 had congenital torticollis. No studies reported any severe adverse event that could be attributed to the BTI. The rate of mild to moderate adverse events reported varied from 5% to 25%. Results regarding efficacy were preliminary, dependent on the pathology, and limited by the small number of studies and their low levels of evidence. CONCLUSIONS: BTI is already widely used as an early treatment for this age group. The safety profile of BTI in infants appears similar to that of older children and risks appear more related to the severity of the pathology and the location of the injections than to the toxin itself. Regarding effectiveness, other studies with higher levels of evidence should be carried out for each specific pathology.

Restricted Range of Motion and a Cold Upper Extremity in a Two-Year-Old Boy: Kaposiform Hemangioendothelioma of the Bone and the Brachial Plexus: A Case Report.

CASE: We report a case of kaposiform hemangioendothelioma (KHE) of the scapula in a 2-year-old boy with motor and sensory abnormalities of the left upper extremity, suggesting brachial plexus involvement. The locally invasive nature prevented resection; sirolimus therapy resulted in improvement of the motor and sensory impairment, as well as decreased tumor size on imaging. CONCLUSION: Osseous infiltration of KHE is known to occur, but its primary presentation in bone without skin involvement is rare and diagnostically challenging. Awareness of rare presentations of KHE, along with accurate histopathologic interpretation, is important to achieve a diagnosis and to differentiate KHE from more common vascular lesions (e.g., infantile hemangioma). Sirolimus therapy is emerging as a promising treatment for unresectable KHE.

Successful Treatment of Brachial Plexopathy Due to Herpes Zoster Infection With Intravenous Immunoglobulin.

OBJECTIVE: The aim of this study was to report the case of a male patient with Parkinson disease who developed brachial plexopathy (BP) due to varicella-zoster virus, which was successfully treated with human immunoglobulin. METHOD: We report the case of a 75-year-old male subject with a diagnosis of Parkinson disease who came to our hospital complaining of pain, skin lesions, and strength loss in his right arm during the past 2 months. Physical examination revealed vesicular rash compatible with varicella-zoster virus lesions. Nerve conduction studies and magnetic resonance imaging of the brachial plexus showed inflammatory changes at that level. A trial with oral valacyclovir followed by intravenous methylprednisolone bolus was administered without further response. However, human intravenous immunoglobulin resulted in complete recovery of the symptoms. CONCLUSIONS: Human immunoglobulin is effective in BP due to zoster infection and must be considered if standard treatment fails. To the best of our knowledge, this is the first report of BP associated to zoster infection successfully treated with intravenous immunoglobulin.

Herpes Zoster Brachial Plexopathy: Direct Steroid Injection.

Herpes zoster (shingles) is a viral disease, characterized by painful skin eruptions and neuropathic sensory symptoms. Motor involvement and brachial plexus involvement in herpes zoster are rare conditions. Together with antiviral medication and pain therapy, palliative and supportive modalities take an important role in the treatment of herpes zoster. It is well documented in previous reports that oral or intravenous steroid administrations may be additive in management. In this case report, positive effects of direct steroid injection onto the brachial plexus via ultrasonography guidance in a patient with motor weakness due to herpes zoster involvement of brachial plexus is presented.

West Nile virus-associated brachial plexopathy.

West Nile virus (WNV) is the most frequent cause of arbovirus infection in the USA. Only 20% of infected individuals are symptomatic. Less than 1% of symptomatic individuals display West Nile neuroinvasive disease. We report a rare case of WNV-associated brachial plexopathy in a young immunocompetent individual, without cerebrospinal fluid pleocytosis or encephalitis. Additionally, there was subjective and objective improvement after high-dose corticosteroids. This case adds to the clinical spectrum of WNV neuroinvasive disease. The literature regarding immunomodulatory treatment and WNV is reviewed.