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Biomedical subjects

John W Miller

Publications and source records attributed to John W Miller.

15 recordsLinked to original sources

Cognitive impairment is not equal in patients with epileptic and psychogenic nonepileptic seizures.

PURPOSE: Patients with psychogenic nonepileptic seizures (PNES) and those with epileptic seizures (ES) purportedly have roughly equal neurocognitive deficits. However, recent findings suggest that patients with somatoform disorders exhibit more variable effort on neurocognitive testing than do controls. We reexamined neurocognitive function in patients with ESs and PNES by using symptom validity testing to control for variability in effort. METHODS: Patients referred for video-EEG monitoring were administered the Word Memory Test (WMT), a measure of symptom validity, as part of neuropsychological evaluation. Patients classified with ictal video-EEG recordings as having ES (n = 41) or PNES (n = 43) were compared on neurocognitive and WMT performance and demographic, psychiatric, and medical variables. RESULTS: Striking rates of WMT failure were observed in the PNES (51.2%) group, but not in the ES (8.1%) group (p = <0.001) after controlling for false-positive errors. Although the PNES and ES groups reported equivalent neurologic histories, the PNES group exhibited less objective evidence of impairment as measured by valid neuropsychological testing, MRI of the brain, and video-EEG monitoring. CONCLUSIONS: Many patients with PNES do not put forth maximal effort during neuropsychological assessment. When patients with PNES put forth valid effort, they demonstrate less objective evidence of neuropathologic injury or disease than do patients with ES. The cognitive impairment reported by this group appears to be more a function of motivational (although not necessarily intentional) factors than of verifiable neuropathology.

Adult↗

Gender differences in handedness and speech lateralization related to early neurologic insults.

Left-handedness is a normal variant but also may result from early-life brain insults. Speech typically resides in the left cerebral hemisphere in normal subjects. In 170 subjects with past brain injuries, bilateral or right hemisphere speech lateralization, determined by the intracarotid amobarbital procedure, was more frequent in females (19 vs 5, p = 0.003) as was left-handedness (26 vs 10, p = 0.004). This could be attributed to greater plasticity or functional symmetry in females.

Age Factors↗

Progression from frontal-parietal to mesial-temporal epilepsy after fluid percussion injury in the rat.

We recently described an in vivo model of post-traumatic epilepsy (PTE) in the rat where chronic spontaneous recurrent seizures appear following a single episode of fluid percussion injury (FPI). PTE, studied during the first 2 months post-injury, was focal and seizures originated predominantly from the frontal-parietal neocortex at or around the injury site. However, rarer bilateral seizures originating from a different and undefined focus were also observed. To shed light on the Posttraumatic Epileptogenic mechanisms and on the generation of bilateral seizures, we studied rats up to 7 months post-injury. In vivo paired epidural and depth-electrode recordings indicated that the anterior hippocampus evolves into an epileptic focus which initiates bilateral seizures. The rate of frontal-parietal seizures remained constant over time after 2 weeks post-injury, while the rate of hippocampal seizures greatly increased over time, suggesting that different mechanisms mediate neocortical and hippocampal post-traumatic epileptogenesis. Because of different temporal evolution of these foci, the epileptic syndrome was characterized by predominant frontal-parietal seizures early after injury, but by predominant mesio-temporal seizures at later time points. Pathological analysis demonstrated progressive hippocampal and temporal cortex pathology that paralleled the increase in frequency and duration of bilateral seizures. These results demonstrate that FPI-induced frontal-parietal epilepsy (FPE) progresses to mesial-temporal lobe epilepsy (MTLE) with dual pathology. These observations establish numerous similarities between FPI-induced and human PTE and further validate it as a clinically relevant model of PTE.

Animals↗

Ictal head version in generalized epilepsy.

Focal physical signs may occur with generalized seizures. The authors retrospectively reviewed video-EEG studies of 20 patients with apparent primary generalized epilepsy to assess the frequency of head version during generalized tonic-clonic seizures. Five patients (25%) demonstrated forced head version, including two with turning to the right and left on consecutive seizures. Forced head turning can occur in generalized epilepsy and may not necessarily indicate focal seizure origin.

Adolescent↗

Determination of language dominance with near-infrared spectroscopy: comparison with the intracarotid amobarbital procedure.

PURPOSE: To determine the efficacy of near-infrared spectroscopy (NIRS) in identifying the hemisphere associated with language by measuring changes in bilateral lateral inferior frontal blood flow during a word generation task in epilepsy surgery patients and healthy volunteers. METHODS: Sixteen patients who underwent the intracarotid amobarbital procedure (IAP) and eight healthy right-handed/right-footed individuals were tested with NIRS during a word generation paradigm. RESULTS: Increases in lateral inferior frontal total hemoglobin concentrations agreed with the IAP in 11 of 16 patients, including 2 of 3 with right hemisphere (atypical) speech dominance (P = 0.13). NIRS revealed increases in lateral inferior frontal total hemoglobin concentrations congruent with language dominance predicted by handedness/footedness in 18 of 24 subjects, including 100% of healthy right-handed subjects (P = 0.02). CONCLUSION: NIRS is a simple, non-invasive, safe modality for measuring cerebral blood flow. Further research and development of testing procedures and instrumentation are needed before routine implementation in pre-surgical testing.

Adult↗

Does glucocorticoid administration prevent late seizures after head injury?

PURPOSE: Preventing posttraumatic epilepsy has been a difficult challenge. In this study we evaluated the association between glucocorticoid administration after traumatic brain injury (TBI) and posttraumatic seizures. METHODS: We examined a seizure-prevention trial database of 404 patients with severe TBI for exposure to glucocorticoids in the early (<1 week) posttraumatic period. After controlling for seizure risk, we compared the odds of developing first and second late posttraumatic seizures between those that received glucocorticoids and those that did not. RESULTS: Patients dosed with glucocorticoids within 1 day of their TBI were more likely to develop first late seizures than were those without [p = 0.04; hazard ratio = 1.74; 95% confidence interval (CI), 1.01-2.98]; whereas those receiving glucocorticoids > or =2 days after their injury had no similar association (p = 0.66; hazard ratio = 0.77; 95% CI, 0.23-2.56; p = 0.10 among the three groups). Receiving glucocorticoids within 1 day, or > or =2 days after TBI was not associated with second late seizure development. CONCLUSIONS: Glucocorticoid treatment after TBI is not associated with decreased late posttraumatic seizures, and early treatment is associated with increased seizure activity.

Adult↗

Post-traumatic epilepsy following fluid percussion injury in the rat.

The lack of an adequate model of post-traumatic epilepsy (PTE), in which, similarly to the human condition, chronic spontaneous focal seizures follow a single episode of traumatic brain injury, has hampered the identification of clinically relevant epileptogenic mechanisms and the development of effective therapies. We studied the electrophysiological, behavioural and structural consequences of a clinically relevant model of closed head injury, the lateral fluid percussion injury (FPI), in the rat. We found that a single episode of severe FPI is sufficient to cause PTE. Chronic electrocorticography (ECoG) demonstrated spontaneous chronic seizures that were partial, originated from the neocortex at the site of injury, and progressively worsened and spread over time. The cases of epilepsy in the post-traumatic population increased over time following injury. Post-FPI epileptic rats exhibited pauses in their behaviour, facial automatisms and myoclonus at the time of epileptiform ECoG events. In vitro local field potential recordings demonstrated persistent hyperexcitability of the neocortex at and around the site of injury that was associated with intense glial reactivity. These results for the first time demonstrate persistent hyperexcitability of the injured neocortex and define a useful model for pathophysiological studies of basic mechanisms of spontaneous epileptogenesis and for preclinical screening of effective antiepileptogenic drugs.

Animals↗

Treatment of out-of-hospital status epilepticus with diazepam rectal gel.

Intravenous access cannot always be promptly obtained when treating status epilepticus outside the hospital. We compared the efficacy and safety of diazepam rectal gel to IV lorazepam in our long-term care facility for adults with developmental disabilities. Diazepam rectal gel was given more quickly and reliably, reducing total seizure time, potential neuronal injury and other complications. A treatment protocol for treating status epilepticus with diazepam rectal gel is given.

Administration, Rectal↗

Factors predicting outcome of surgery for intractable epilepsy with pathologically verified mesial temporal sclerosis.

PURPOSE: To examine the subgroup of patients with medically intractable epilepsy receiving temporal lobectomies who have pathologically verified mesial temporal sclerosis (MTS) and to determine the relation of demographic and clinical factors, results of diagnostic testing, and details of the surgical procedure with prognosis for achieving control of seizures. METHODS: All patients receiving surgical treatment for intractable epilepsy between 1991 and 1998 at the University of Washington were reviewed. There were 118 patients who met inclusion criteria of adequate pathological analysis showing MTS without a progressive process and a minimum of 1-year follow-up. RESULTS: Only personal history of status epilepticus demonstrated significant (p = 0.0276) prediction of outcome, increasing the risk of surgical failure. No other factors were significant predictors of outcome, including history of febrile seizures, possible etiologic factors, EEG, magnetic resonance imaging (MRI) or neuropsychological testing results, or extent of resection. CONCLUSIONS: Many factors that have been previously described to predict favorable outcome in the overall group of patients receiving temporal lobe resections for intractable epilepsy are, in fact, predictors of MTS and lose their predictive value when the subgroup of patients with confirmed MTS is examined. Neurosurgical treatment of MTS can be very effective even in the presence of significant etiologic factors, or of bilateral or extratemporal abnormalities on EEG or MRI.

Adult↗

Retinal lesions as clues to disseminated bacterial and candidal infections: frequency, natural history, and etiology.

Invasive bacterial and candidal infections are known to involve the retina, but the natural history of the retinal lesions and the utility of ophthalmologic consultation in the critical care setting as a diagnostic tool are not well understood. We 1) performed weekly funduscopic examinations on 77 medical and surgical patients in intensive care units (ICUs), 2) analyzed results of serial ocular examinations in 180 non-neutropenic patients with candidemia, and 3) reviewed the English literature on the association of retinal lesions with disseminated bacterial or candidal infection (DBCI). We found that 15 (19%) of the ICU patients had retinal lesions consistent with DBCI. Of these 15, 1 had clearly sepsis-related retinal lesions, while 13 (87%) had 1 or more systemic disease that could have explained their retinal findings (6 diabetic retinopathy; 2 human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) retinopathy; 2 hypertensive retinopathy; 1 hemolytic uremic syndrome, and 1 leukemia). Multivariate analysis revealed that systemic disease (odds ratio 8.37, 95% confidence intervals: 3.24-21.56) independently correlated with the presence of retinal lesions while DBCI, trauma, hyperalimentation, and transfusion of blood products were not independently predictive in any analysis. Twenty of the 180 (15%) candidemic patients had retinal lesions. Two (1%) had classic 3-dimensional white lesions with vitreal extension, and 5 (2.7%) had chorioretinal lesions without vitreal haziness. Notably, 10% of patients had superficial retinal hemorrhages and/or cotton wool spots that could have been due to either candidemia or a systemic disease (diabetes, hypertension, renal failure, closed head trauma). Concurrent bacteremia occurred in 3 of the 27 patients with eye lesions. Retinal lesions resolved in a mean of 33 days. None of the patients had symptoms at the time of the retinal finding. We found 3 studies that prospectively assessed retinal lesions in bacteremic patients. The frequency of retinal lesions in these series varied from 12% to 26%, with the most common lesions being cotton wool spots followed by superficial retinal hemorrhages. White-centered hemorrhages were seen in about 15% +/- 2 of bacteremic patients. Five studies prospectively evaluated candidemic patients for Candida endophthalmitis. These studies observed rates from 0% to 78% for lesions consistent with candidal endophthalmitis. Most studies performed recently found that nonspecific lesions such as cotton wool spots or superficial retinal hemorrhages occurred with a frequency of 11% to 20%. The availability of less toxic antifungal agents, more frequent use of empirical therapy, and the trend to early treatment may be altering the frequency of this complication. Observation of a classic 3-dimensional retina-based vitreal inflammatory process is virtually diagnostic of endogenous endophthalmitis due to Candida spp., but such lesions are relatively uncommon. Conversely, nonspecific lesions that could be due to bacterial or candidal endophthalmitis (cotton wool spots, retinal hemorrhages, and Roth spots) are seen frequently. These lesions are most often due to an underlying systemic disease rather than an infection. Serial examinations provide the best evidence that a given lesion is due to an intercurrent infection. The current low rate of vitreal extension of retinal process appears to be due to the high rate of empirical or therapeutic use of antifungal agents in high-risk patient groups. Ophthalmoscopy should be performed in patients with known candidemia. However, ophthalmoscopic examination seems to have little value in assisting with the discovery of occult disseminated candidiasis or bacterial infection.

Adult↗

Vagal nerve stimulation induces intermittent hypocapnia.

PURPOSE: To study whether respiratory alteration caused by vagal nerve stimulation (VNS) can change end-tidal carbon dioxide (EtCO2) levels. METHODS: We performed polygraphic recordings including capnographic monitoring during daytime sleep on adults with VNS therapy. RESULTS: Ten of 13 patients showed VNS-induced alterations in the frequency or amplitude of respiration. Five patients had a consistent increase in respiratory rate with a simultaneous, consistent and significant decrease (p < 0.01; 5-22%) in EtCO2 during VNS. Three subjects showed occasional decreases in EtCO2 during VNS, and two showed no clearly detectable VNS-related EtCO2 changes. CONCLUSIONS: Our findings suggest that VNS may alter brain CO2 levels through changes in respiration. Because carbon dioxide (CO2) has potent effects on various brain functions, it is possible that these transient CO2 changes may have an effect on the state transitions between interictal and preictal states.

Adult↗

Do nonspecific focal EEG slowing and epileptiform abnormalities favor one hemisphere?

PURPOSE: Several EEG-based studies suggest that epileptiform activity originates from the left more than the right hemisphere. In contrast, other pathophysiologies such as stroke lateralize relatively symmetrically. Study of focal slowing and other EEG abnormalities allows assessment of favoring as well as referral and interpretation bias. METHODS: The 1,331 consecutive adult EEG reports were reviewed for epileptiform discharges (EDs) and nonepileptiform focal slowing. Side of slowing or EDs, interpreting electoencephalographer, and whether the patient was undergoing long-term monitoring or routine EEG were tallied. Results were statistically analyzed. RESULTS: Focal slowing occurred symmetrically; EDs favored the left hemisphere (p < 0.01). CONCLUSIONS: The left hemisphere may be more prone to epileptiform abnormalities in adults, but not to the nonspecific pathophysiologic processes that cause slowing. These findings suggest that potential interpretation bias does not influence left hemispheric favoring of EDs and instead may implicate a biologic etiology.

Adult↗

The experience of earthquakes by patients with epileptic and psychogenic nonepileptic seizures.

PURPOSE: We sought to understand better the experience of seizures by studying differences in the subjective experience of being in an earthquake between patients with epileptic (EP) and nonepileptic (NES) seizures. METHODS: Forty-eight patients with CCTV/EEG-documented EP or NES who were in the Seattle metropolitan area during the February 28, 2001 Nisqually earthquake were randomly selected for telephone interviews on their earthquake experiences, including whether they thought they were having a seizure during the event. RESULTS: Twenty-three percent of EP patients spontaneously volunteered that they initially thought they were having a seizure during the earthquake as compared with none of the NES individuals (p = 0.03). However, 35% of EP and 23% of NES patients thought they were having a seizure during it when asked directly (p = 0.37). The most common reasons given, regardless of seizure type, were shaking and feelings of losing control. Of those responding negatively, 100% of EP and 47% of NES patients said that movement of their environment indicated that it was not a seizure (p = 0.001). EP patients took an average of 42 s to realize that the earthquake was not a seizure compared with 105 s for the NES group (p = 0.06). The earthquake precipitated seizures in both groups (11.5% EP, 9.1% NES). CONCLUSIONS: EP patients were more likely to mistake the earthquake spontaneously for a seizure. This indicates these two experiences are similar and provides a glimpse into the subjective experience of a seizure for those who have never had one but have experienced an earthquake.

Adult↗

Ginkgo biloba: evaluation of CYP2C9 drug interactions in vitro and in vivo.

Ginkgo biloba extract is one of the most widely used herbal products in the United States. However, bleeding episodes in patients taking Ginkgo biloba and warfarin have been documented. Therefore, in vitro and in vivo inhibition studies were done to ascertain the influence of ginkgo on CYP2C9, the P-450 isozyme responsible for the metabolism of the most potent warfarin enantiomer, (S)-warfarin. Ginkgo extract inhibited human liver microsomal CYP2C9 with an apparent Ki=14.8 microg/mL, and the inhibition was increased by acid hydrolysis (apparent Ki=9.1 microg/mL). Two open-label, crossover pharmacokinetic studies in healthy subjects were performed using tolbutamide and diclofenac as probe CYP2C9 substrates. In contrast to the in vitro inhibition of CYP2C9, no interactions between Ginkgo biloba extract and CYP2C9 probe substrates were observed in vivo as evidenced by the lack of effect on the steady-state pharmacokinetics of diclofenac or on the urinary metabolic ratio of tolbutamide.

Adult↗