Malignant Glial Neuronal Tumors After West Nile Virus Neuroinvasive Disease: A Coincidence or a Clue?

Following acute West Nile virus (WNV) infection in humans, there is upregulation of pro-inflammatory molecules that promote neuroinflammation, including S100 calcium binding protein B (S100B), high-mobility group box-1 (HMGB1), and osteopontin (OPN). The effects of S100B and HMGB1 are transduced by the receptor for advanced glycation end products (RAGE). Interestingly, the same immunoregulatory proteins that fuel neuroinflammation can also promote tumorigenesis. We present 2 cases of glial neuronal tumors, a glioblastoma multiforme and dysembryoplastic neuroepithelial tumor, in patients with severe West Nile neuroinvasive disease (WNND). In these cases, the viral infection was a precursor to the development of the aggressive brain tumors. We describe a potential mechanism where the presence of tumorigenic proteins in the microenvironment induced by WNV, and subsequent RAGE and OPN signaling, may contribute to development or aggressive growth of these tumors. Although it is certainly possible that the occurrence of primary brain tumors following WNND is coincidental, the ability of WNV to alter cellular signaling and increase expression of pro-inflammatory and tumorigenic molecules merits further investigations to determine whether there is an association between these disease processes or implications for brain tumor patients who develop WNV infection.

Acute transverse myelitis - A rare clinical manifestation of Lyme neuroborreliosis.

Acute transverse myelitis (ATM) is a rare, potentially devastating neurological syndrome that has variety of causes, infectious being one of them. Lyme disease (LD) is the most common vector borne zoonosis in the United States (U.S.). While neurologic complications of LD are common, acute transverse myelitis is an exceedingly rare complication. We present a case of a previously healthy 25-year-old man who presented with secondary erythema migrans, aseptic meningitis and clinical features of transverse myelitis including bilateral lower extremity motor and sensory deficits manifesting as weakness and numbness, urinary retention and constipation. Despite negative serum antibodies against Borrelia burgdoferi, cerebrospinal fluid (CSF) was positive for Borrelia burgdorferi PCR. Following treatment with methylprednisolone and ceftriaxone, he attained complete recovery apart from neurogenic bladder necessitating intermittent self-catheterization. We report rare manifestation of a common disease and emphasize the importance of considering LD in the differential diagnosis of acute transverse myelitis, particularly in residents of endemic areas.

Topiramate for Treatment in Patients With Migraine and Epilepsy.

BACKGROUND: Antiepileptic drugs (AED) are often considered first line for monotherapy in treatment of patients with migraines, and also those with comorbid migraine and epilepsy. Topiramate, a newer generation AED, has broad mechanism of action and evidence of benefit in patients with either episodic or chronic migraine along with epilepsy, both generalized and focal. METHODS: Our goal is to review the relevant mechanisms of action along with any supportive evidence published to date on the use of topiramate (TPM) in patients with both migraine headache and epilepsy. CONCLUSIONS: There has been very little published to date on the use of TPM in patients diagnosed with both disorders. Despite this, TPM has been adopted as first line therapy in this patient population. Future studies investigating the effectiveness of this treatment strategy are warranted in order to determine the most effective use of this medication in patients diagnosed with migraine headaches and epilepsy.

Fall prevention and bathroom safety in the epilepsy monitoring unit.

Falls are one of the most common adverse events occurring in the epilepsy monitoring unit (EMU) and can result in significant injury. Protocols and procedures to reduce falls vary significantly between institutions as it is not yet known what interventions are effective in the EMU setting. This study retrospectively examined the frequency of falls and the impact of serial changes in fall prevention strategies utilized in the EMU between 2001 and 2014 at a single institution. Overall fall rate was 2.81 per 1000 patient days and varied annually from 0 to 9.02 per 1000 patient days. Both seizures and psychogenic nonepileptic events occurring in the bathroom were more likely to result in falls compared with events occurring elsewhere in the room. With initiation of increased patient education, hourly nurse rounding, nocturnal bed alarms, having two persons assisting for high fall risk patients when out of bed, and immediate postfall team review between 2001 and 2013, there was a trend of decreasing fall frequency; however, no specific intervention could be identified as having a particular high impact. In late 2013, a ceiling lift system extending into the bathroom was put in place for use in all EMU patients when out of bed. In the subsequent 15 months, there have been zero falls. The results reinforce both the need for diligent safety standards to prevent falls in the EMU as well as the challenges in identifying the most effective practices to achieve this goal.

Amantadine for patients with severe traumatic brain injury: a critically appraised topic.

BACKGROUND: Research into traumatic brain injury (TBI) has increased significantly. Diagnostic testing and therapeutics for patients with severe TBI are 2 areas on which there is increasing focus. Amantadine hydrochloride is one treatment considered to have potential therapeutic value in this patient population. OBJECTIVE: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the disciplines of neurocritical care and physical medicine and rehabilitation. RESULTS: A multicenter, placebo-controlled, double-blind, randomized controlled trial was selected for review. The trial compared the rate of recovery, as determined by the overall Disability Rating Scale score, in a total of 184 patients with severe TBI. Patients were randomized to either receive amantadine (87) or visually identical placebo (97) over the 4-week study interval. The rate of recovery, as measured by the Disability Rating Scale, was found to be greater in the treatment arm as compared with the placebo arm (difference in slope -0.24 points/wk, P=0.007) over the 4-week treatment interval. CONCLUSIONS: The results from this study demonstrated that amantadine hydrochloride accelerates recovery in patients with severe TBI.

The influence of staffing on diagnostic yield of EMU admissions: a comparison study between two institutions.

Patients with recurrent, stereotyped neurological events of unclear etiology often warrant admission for continuous video-EEG monitoring in an epilepsy monitoring unit (EMU) for diagnosis. Epilepsy monitoring unit admission duration has been reported to range from days to weeks. To date, there are limited data on the average duration of admission for patients admitted to the EMU for spell classification. Many EMUs are forced to limit the overall duration of admission for numerous reasons including limited resources. It is unclear if a time-limited EMU stay reduces the event capture rate and, therefore, diagnostic yield of event classification admissions. The goal of this study was to determine how a time-limited length of stay strategy impacted event capture in patients admitted for spell classification. A retrospective chart review was performed at two comparable adult epilepsy monitoring units, Mayo Clinic Hospital (MCH) in Phoenix, Arizona, and Banner Good Samaritan Medical Center (BGSMC) in Phoenix, Arizona. Banner Good Samaritan Medical Center is only staffed Monday through Friday, thereby limiting the total possible duration of admission to five days. The goal was to determine if the rate of event capture differed between two institutions employing a time-limited EMU admission (BGSMC) when compared with the nonlimited admission (MCH). A total of 300 patient admissions at MCH and 260 patient admissions at BGSMC were reviewed over a comparable time period. The event capture rates at MCH and BGSMC were 74% and 72%, respectively. There was a greater percentage of patients with nonepileptic events (NEEs) at MCH than at BGSMC (62.7% vs. 47.3%). The mean duration until first event was 31h at MCH and 38 h at BGSMC. The mean length of stay was greater at MCH (4.5 days) when compared with BGSMC (3.3 days). The overall diagnostic yield of a time-limited EMU admission was similar to that of a nonlimited admission for the purpose of spell classification. There was a statistically significant difference when comparing the time until first event at both institutions; however, this still fell within the 5-day duration that the time-restricted admission was limited to. These results may be important in optimizing an EMU practice in patients requiring admission for spell classification.

Autonomic dysfunction in adult-onset alexander disease: a case report and review of the literature.

BACKGROUND: Alexander disease (AxD) is an astrogliopathy, resulting from a mutation in the glial fibrillary astrocytic protein gene. Different clinical subtypes have been described, including infantile, juvenile, and adult onset, based upon the age at which symptoms begin. Patients with the adult-onset form, develop a progressive, spastic paraparesis, palatal myoclonus, ataxia, and bulbar weakness. Autonomic nervous system (ANS) dysfunction has been reported as a potential manifestation of adult-onset AxD, but has not been well characterized. OBJECTIVE: We report a case of adult-onset AxD with symptomatic orthostatic hypotension (OH) and heat intolerance that underwent formal autonomic testing. In addition, a comprehensive literature search was conducted to review the frequency and pattern of autonomic dysfunction in this patient population. RESULTS: A 51-year-old patient was diagnosed with AxD at the age of 47, following an 8-year history of vertigo, intermittent diplopia, and sleep disturbance. The patient developed symptoms of OH, erectile dysfunction, and heat intolerance soon after his diagnosis. Autonomic testing demonstrated OH on tilt-table testing (47 mmHg decrease in BP with 18 BPM heart rate increment) with absent late phase II and IV responses during the Valsalva maneuver, severe cardiovagal impairment, and preserved postganglionic sympathetic sudomotor function. These findings were interpreted as being consistent with central autonomic failure. The most common autonomic symptoms reported in other AxD cases include constipation, urinary incontinence, and sphincter dysfunction. To our knowledge, this is the first report of formal autonomic testing in AxD. CONCLUSION: Signs and symptoms of ANS impairment can occur in patients with AxD, and can include orthostatic hypotension and bowel/bladder dysfunction. Autonomic testing in our patient suggests impairment in central autonomic pathways.

Determination of hemispheric language dominance in the surgical epilepsy patient: diagnostic properties of functional magnetic resonance imaging.

BACKGROUND: Presurgical evaluation for refractory epilepsy typically includes assessment of cognitive and language functions. The reference standard for determination of hemispheric language dominance has been the intracarotid amobarbital test (IAT) but functional magnetic resonance imaging (fMRI) is increasingly used. OBJECTIVE: To critically assess current evidence regarding the diagnostic properties of fMRI in comparison with the IAT for determination of hemispheric language dominance. METHODS: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the fields of epilepsy and neurosurgery. RESULTS: A systematic review and meta-analysis that compared the sensitivity and specificity of fMRI to IAT-determined language lateralization was selected for critical appraisal. The review included data from 23 articles (n=442); study methodology varied widely. fMRI was 83.5% sensitive and 88.1% specific for detection of hemispheric language dominance. CONCLUSIONS: There are insufficient data to support routine use of fMRI for the purpose of determining hemispheric language dominance in patients with intractable epilepsy. Larger, well-designed studies of fMRI for language and other cognitive outcomes as part of the presurgical and postsurgical evaluation of epilepsy patients are necessary.

Ganglion cell regeneration following whole-retina destruction in zebrafish.

The retinas of adult teleost fish can regenerate neurons following injury. The current study provides the first documentation of functional whole retina regeneration in the zebrafish, Danio rerio, following intraocular injection of the cytotoxin, ouabain. Loss and replacement of laminated retinal tissue was monitored by analysis of cell death and cell proliferation, and by analysis of retina-specific gene expression patterns. The spatiotemporal process of retinal ganglion cell (RGC) regeneration was followed through the use of selective markers, and was found to largely recapitulate the spatiotemporal process of embryonic ganglion cell neurogenesis, over a more protracted time frame. However, the re-expression of some ganglion cell markers was not observed. The growth and pathfinding of ganglion cell axons was evaluated by measurement of the optic nerve head (ONH), and the restoration of normal ONH size was found to correspond to the time of recovery of two visually-mediated behaviors. However, some abnormalities were noted, including overproduction of RGCs, and progressive and excessive growth of the ONH at longer recovery times. This model system for whole-retina regeneration has provided an informative view of the regenerative process.