Diffusivity measurements differentiate benign from malignant lesions in patients with peripheral neuropathy or plexopathy.

BACKGROUND AND PURPOSE: Peripheral nerve disorders caused by benign and malignant primary nerve sheath tumors, infiltration or compression of nerves by metastatic disease, and postradiation neuritis demonstrate overlapping features on conventional MR imaging but require vastly different therapeutic approaches. We characterize and compare diffusivities of peripheral nerve lesions in patients undergoing MR neurography for peripheral neuropathy or brachial or lumbosacral plexopathy. MATERIALS AND METHODS: Twenty-three patients, referred for MR neurography at our institution between 2003 and 2009 for a peripheral mononeuropathy or brachial or lumbosacral plexopathy and whose examinations included DWI, received a definitive diagnosis, based on biopsy results or clinical and imaging follow-up, for a masslike or infiltrative peripheral nerve or plexus lesion suspicious for tumor. Mean ADC values were determined within each lesion and compared across 3 groups (benign lesions, malignant lesions, and postradiation changes). RESULTS: Both ANOVA and Kruskal-Wallis tests demonstrated a statistically significant difference in ADC values across the 3 groups (P = .000023, P = .00056, respectively). Post hoc pair-wise comparisons showed that the ADC within malignant tumors differed significantly from that within benign tumors and postradiation changes. ADC within benign tumors and postradiation changes did not differ significantly from each other. CONCLUSIONS: DWI may be highly effective for the differentiation of benign from malignant peripheral nerve masslike or infiltrative lesions.

Calcium-binding protein (calbindin-D28K) and parvalbumin immunocytochemistry in the normal and epileptic human hippocampus.

The calcium-binding proteins calbindin-D28K (CaBP) and parvalbumin (PV) were localized in the "normal" and "epileptic" human hippocampus to address the possible relationship between the expression of these constitutive cytosolic calcium-binding proteins and the resistance or selective vulnerability of different hippocampal neuron populations in temporal lobe epilepsy. Compared to rodents and a baboon (Papio papio), the pattern of CaBP-like immunoreactivity (LI) in the "normal" human hippocampus is unique. CaBP-LI is present in the dentate granule cells, neurons of the "resistant zone" (area CA2), and presumed interneurons of all regions. Unlike rodent and baboon CA1 pyramidal cells, human CA1 pyramidal cells appear to be devoid of CaBP-LI. Thus, the relatively resistant dentate granule cells and CA2 pyramidal cells are the only human hippocampal principal cells that contain CaBP-LI normally. As in lower mammals, PV-LI is present exclusively in interneurons of all human hippocampal subregions. CaBP- and PV-LI were localized in hippocampi surgically removed in the treatment of intractable temporal lobe epilepsy to determine whether surviving hippocampal cells were those that express these calcium-binding proteins. Hippocampi removed from patients with tumors or arteriovenous malformations that were associated with complex partial seizures arising from this region appeared relatively normal histologically. CaBP- and PV-LI in this patient group appeared similar to that seen in autopsy controls. Conversely, "cryptogenic" epileptics, who exhibit hippocampal sclerosis as the only lesion associated with the epilepsy, exhibited a preferential survival of hippocampal cells that were CaBP- or PV-immunoreactive. In the dentate hilus, which normally contains few CaBP-LI neurons, most of the few surviving hilar neurons were CaBP-immunoreactive. Their number and darkness of staining suggests that CaBP synthesis may be increased in cells that survive. Despite an obvious decrease of PV-LI specifically in the damaged parts of the sclerotic hippocampi, PV-immunoreactive interneurons were often among the few surviving cells. Nevertheless, large expanses of the surviving granule cell layer appeared to have lost the PV-immunoreactive axosomatic fiber plexus. These results reveal a unique and striking correlation between the human hippocampal cells that normally express these calcium-binding proteins and those that survive in the sclerotic epileptic hippocampus.

Effect of pallidotomy on postural control and motor function in Parkinson disease.

OBJECTIVE: To investigate the effects of pallidotomy on postural reactions and other motor parkinsonian deficits. DESIGN: Comparison of performance by patients before and after pallidotomy on tests of balance and function. SETTING: A Parkinson disease Center of Excellence and Center for Human Performance Testing at a university hospital and research center. PARTICIPANTS: Twenty-nine patients with Parkinson disease undergoing pallidotomy. MAIN OUTCOME MEASURES: Performance results on the United Parkinson's Disease Rating Scale (UPDRS), activities of daily living and motor subscales (parts II and III). and posturography (sensory organization test), which were collected before and 3 and 6 months after surgery with patients in the practically defined off state (medication withheld for at least 12 hours). RESULTS: Data were analyzed with a paired Wilcoxon and Spearman correlation. There was a significant improvement in mean +/- SD UPDRS motor subscale score after pallidotomy (before surgery, 52.43+/-13.46; after surgery, 43.93+/-15.15; z= 3.63; P=.003). There were no significant changes in the UPDRS activities of daily living subscale or average stability scores when the group was examined as a whole. However, examination of individual data revealed that 9 (56%) of 16 patients who could stand independently before surgery showed improvement in either the number of falls or the average stability score. No patient who was unable to stand independently before surgery was able to stand independently after it. CONCLUSION: Pallidotomy helped improve overall motor function in patients with parkinsonism and, for some patients, also improved postural stability.

Phosphatidylserine-dependent phagocytosis of apoptotic glioma cells by normal human microglia, astrocytes, and glioma cells.

Apoptotic cells display signals that trigger phagocytic removal by macrophages or neighboring cells. To better understand the signals triggering phagocytosis of apoptotic glioma cells, and to identify the cells that might be involved in the phagocytic process, U-251 MG glioma cells were made apoptotic by etoposide (25 microg/ml) treatment and were incubated with normal human astrocytes (NHA), glioma cells, or microglia. Extent of phagocytosis was assessed by an in vitro phagocytosis assay. After 3 h of incubation with apoptotic cells, phagocytes tested were washed to remove nonengulfed cells, then fixed, stained, and counted to determine phagocytosis index (PI). NHA, glioma cells, and microglia all phagocytosed apoptotic, but not nonapoptotic, glioma cells. Microglia, however, had a PI approximately 4-fold higher than did either NHA or glioma cells. Binding of phosphatidylserine (PS) on apoptotic glioma cell membranes by annexin-V inhibited phagocytosis by 90% in both microglia and NHA. The activity of an enzyme (scramblase) that moves PS from the inner cell membrane to the outer cell membrane was also increased in apoptotic glioma cells. These results suggest that a variety of cells present in and near gliomas in vivo can remove glioma cells in a PS-dependent scramblase-mediated fashion. Manipulation of scramblase and/or PS exposure in glioma cells may therefore be a means of triggering phagocytic removal of glioma cells.

The prognostic value of postoperative seizures following epilepsy surgery.

Among 55 patients undergoing temporal lobectomy for refractory epilepsy, patients with seizures in the week following surgery had a poor long-term, seizure-free outcome compared with patients without seizures. Outcome for patients with single seizures or seizures restricted to the first postoperative day seemed favorable compared with patients with multiple or later seizures. Seizure type and similarity to preoperative events did not predict outcome.

Frequency and characteristics of visual field deficits after surgery for mesial temporal sclerosis.

In a series of 33 patients undergoing tailored temporal lobe resection for mesial temporal sclerosis, the frequency of postoperative visual field deficit (VFD) was 52%. The size and configuration were similar after operation in the right and left hemispheres. We observed partial upper quadrantanopias in 16 of 28 patients who became seizure-free and in only one of five patients with residual seizures. VFDs may provide an independent measure of the functional extent of resection.

False lateralization by subdural electrodes in two patients with temporal lobe epilepsy.

The authors present two patients with medically refractory partial seizures who had invasive recordings with stereotactic depth EEG (SEEG) and subdural electrodes (SDE) as part of their presurgical workup. SDE recordings were falsely lateralizing in both of these patients with pathologically proven mesial temporal sclerosis. In temporal lobe epilepsy, SEEG electrodes should be considered when presurgical studies are discordant.

Temporal lobectomy for epilepsy: recovery of the contralateral hippocampus measured by (1)H MRS.

(1)H MRS imaging was obtained from 10 patients with mesial temporal lobe epilepsy before and after surgery. After surgery, metabolic recovery in the contralateral hippocampus was detected. Preoperatively, reduced N-acetylaspartate (p < 0.04) increased after surgery nonsignificantly to equal control values. Cholines increased after surgery (p < 0.02) and creatine-phosphocreatine showed a trend to higher values. The results suggest that the contralateral hippocampus is affected by repeated seizure activity in the ipsilateral hippocampus, rather than presence of bilateral mesial temporal sclerosis.

1H MRSI predicts surgical outcome in MRI-negative temporal lobe epilepsy.

1H MRS imaging (MRSI) was performed on 15 patients with MRI-negative temporal lobe epilepsy (TLE) who underwent seizure surgery. The non-seizure-free patients (NSF) ipsilateral hippocampal N-acetylaspartate (NAA)/(Cr+Cho) z scores were lower than the contralateral scores (p = 0.04), and the NSF ipsilateral z scores were lower than the seizure-free patients' (SF) ipsilateral z scores (p = 0.0049). Similarly, NSF contralateral scores were lower than contralateral SF (p = 0.02). These findings suggest NAA predicts the surgical outcome in patients with TLE without evidence of mesial temporal sclerosis on MRI.

Electrophysiologic evaluation of lumbosacral radiculopathies: electromyography, late responses, and somatosensory evoked potentials.

We compared the diagnostic utility of EMG, F wave and H-reflex studies, and peroneal and dermatomal SEPs in evaluating 28 patients with clinically unequivocal L-5 or S-1 compressive root lesions. The single most useful electrophysiologic technique was EMG, which often provided evidence of denervation in a myotomal pattern when other electrophysiologic findings were normal. We found abnormal late responses in 14 patients, but always in association with EMG abnormalities. Peroneal-derived SEPs were always normal. Dermatomal SEPs confirmed the diagnosis in seven patients, including two in whom other electrophysiologic studies were normal.

A potential role for astrocytes in mediating the antiepileptic actions of furosemide in vitro.

Epileptic seizures are characterized by abnormal electrical discharge. In previous studies we established a powerful antiepileptic action for a commonly used diuretic (furosemide). However, it remains unclear precisely how furosemide terminates abnormal electrical discharges. To address this issue, we performed in vitro experiments to examine conditions where furosemide exerts antiepileptic activity and patch-clamp studies to analyze the effect of furosemide on neuronal membrane properties, synaptic function and inward potassium current. Furosemide was not found to alter synaptic field responses, excitatory postsynaptic currents or intrinsic membrane properties of principal hippocampal neurons. Our in vitro studies indicate that furosemide does not abolish spontaneous epileptiform bursting during co-application of Ba2+ or Cs+ ions (to block inwardly rectifying potassium channels). Our patch-clamp data indicate that furosemide enhances the function of astrocytic, but not neuronal, inward potassium channels and that this modulation may be required for its antiepileptic activity. Although a variety of antiepileptic drugs are already available, none of these compounds selectively target astrocytes while preserving synaptic/neuronal function. Thus, furosemide-mediated modulation of inward potassium current (on astrocytes) represents a new target for control of abnormal electrical discharge in the CNS.

Midbrain stimulation inhibits tail-flick only at currents sufficient to excite rostral medullary neurons.

The effects of midbrain electrical stimulation on the activity of tail-flick (TF) related neurons in the rostral ventromedial medulla (RVM) were studied. Neurons whose activity either decreased (off-cells) or increased (on-cells) immediately prior to TF were examined. Of 31 off- and on-cells, 26 (84%) showed increased activity during midbrain stimulation sufficient to suppress the TF. Furthermore, in 21 of these cells, the threshold for activation was identical to the threshold for TF suppression, and in the other 5 cells the threshold difference was less than or equal to 5 microA. This study provides evidence that off-and on-cells in the RVM mediate the antinociceptive actions of midbrain stimulation.

Tail-flick related activity in medullospinal neurons.

Using the classification system of Fields et al. 131 neurons in the rostral ventromedial medulla (RVM) of lightly anesthetized rats were divided into 3 groups according to their response during tail-flick (TF) testing: those with an abrupt increase in activity prior to TF (on-cells); those with a sudden pause in activity prior to TF (off-cells); those with no change in activity prior to TF (neutral cells). Collision testing was performed using a cervical spinal cord stimulating electrode to determine whether these neurons projected to the cord. Conduction velocities were determined for all cord-projecting neurons. All 3 cell types projected to the cord and approximately 38% of cord-projecting neurons were flick-related (off-or on-cells). All projecting neurons were within or immediately adjacent to the nucleus raphe magnus. The mean conduction velocity of on-cell axons (17.7 m/s) was significantly greater than that of off-cell axons (10.7 m/s) and neutral cell axons (12.4 m/s). Conduction velocities for all cells were within the range for myelinated axons. These findings support the hypothesis that off-and on-cells in the RVM play a significant role in pain modulation at the spinal cord level.

Spatial and temporal variation of microstimulation thresholds for inhibiting the tail-flick reflex from the rat's rostral medial medulla.

Suppression of the tail-flick reflex by microstimulation of the rostral medial medulla in rats lightly anesthetized with barbiturates was studied with regard to spatial and temporal variations in electrical threshold. Trains of constant-current pulses with linearly descending amplitudes (called 'ramps') were passed through the extracellular brain microelectrode during noxious heating of the tail. The pulse amplitude at the time of the reflex, after allowance for conduction and reaction latencies, was taken as the threshold reading. This new method revealed a range of vertical electrode positions corresponding roughly to the nucleus raphe magnus, where the thresholds tended to be lowest (a mean of 4.1 microA for 0.4-ms pulses delivered at 50 Hz). In confirmation of the technique's validity neither the duration of the ramp nor its starting amplitude, within their useful range, significantly affected the measured threshold. Pronounced temporal fluctuation was seen in thresholds measured every 2 min. Spatial variability within the low-threshold region and differences between preparations were statistically much smaller sources of variation. The temporal fluctuation appeared to have a stationary mean for at least 20 min under constant conditions of anesthesia. In some experiments, action potentials from single neurons were recorded through the stimulating electrode, and classified into those inhibited during the tail-flick (off-cells), those excited (on-cells), and those unaffected (neutral cells). The thresholds where off-cells exhibited their maximum action potential were on average significantly lower than corresponding thresholds for on-cells. Short-range (less than 0.2 mm) spatial variations in the threshold appeared however to be uncorrelated with the distance to an individual recorded off-cell or on-cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Putative pain modulating neurons in the rostral ventral medulla: reflex-related activity predicts effects of morphine.

Three physiologically-defined classes of neurons are found in the rostral ventromedial medulla (RVM), a region which contributes to the antinociceptive action of opiates. The off-cell exhibits an abrupt pause just prior to the occurrence of the tail flick reflex (TF). The on-cell shows a burst of activity beginning just prior to the occurrence of the TF. Neutral cell firing does not change in relation to the TF. Systemic administration of morphine has been shown to produce a consistent increase in the activity of off-cells. In the present studies, the effects of systemically-administered morphine on spontaneous and TF-related activity of on-cells and neutral cells were examined in lightly-anesthetized rats. Measures of spontaneous activity were obtained before and after morphine (1.25-2.5 mg/kg, i.v.). On-cells exhibited an irregular cyclic rate of spontaneous discharge similar to that previously reported for off-cells. In contrast, neutral cells had a nearly constant level of spontaneous activity. After administration of morphine, spontaneous activity ceased for 8 of 8 on-cells, and heat-related activity was eliminated. Administration of naloxone resulted in a return of the periodic firing pattern and the burst associated with the TF. Seven of 8 neutral cells showed no change in firing rate and one showed a decrease rate after morphine administration. These results show that the effect of systemic opiates on an RVM neuron can be predicted based on whether a cell increases or decreases its firing just prior to the occurrence of a nocifensive reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphine analgesia and acute physical dependence: rapid onset of two opposing, dose-related processes.

Enhanced responsiveness to noxious stimulation is a reliable sign of opioid withdrawal and is therefore a measure of physical dependence. In lightly anesthetized rats, naloxone, given i.v. 15 min following i.v. morphine, caused a significant shortening of tail flick latency (hyperalgesia). At each dose of naloxone (0.1, 1.0 or 2.0 mg/kg), the magnitude of the observed hyperalgesia was a function of the preceding dose of morphine (0.5, 1.0 or 2.0 mg/kg). Thus morphine rapidly induces two dose-related opposing processes: one results in antinociception and the other in the potential for hyperalgesia.

Effects of intrathecally administered methysergide and yohimbine on microstimulation-produced antinociception in the rat.

This study examined whether intrathecal (i.t.) administration of the serotonergic antagonist methysergide, of the alpha 2 noradrenergic antagonist yohimbine, or of both drugs antagonized stimulation-produced antinociception (SPA) evoked from the nucleus raphe magnus (NRM) and the nucleus reticularis paragigantocellularis (NRPG) of lightly anesthetized rats. The increase in tail flick latency (TFL), but not the increase in paw pinch withdrawal threshold (PWT), evoked from NRM sites was antagonized by i.t. administration of methysergide. Intrathecal administration of yohimbine antagonized both the increase in TFL and the increase in PWT produced by stimulation of NRM sites. Stimulation of sites in the NRPG also increased TFL and PWT; these increases were not antagonized by i.t. administration of methysergide. Although i.t. administration of yohimbine antagonized the increase in TFL evoked from the NRPG, the increase in PWT was not antagonized. When coadministered intrathecally, methysergide and yohimbine antagonized the increases in TFL and PWT produced by stimulation of NRM and of NRPG sites. In contrast, i.v. administration of the same doses of methysergide and yohimbine did not antagonize either the increase in TFL or the increase in PWT evoked from either set of sites. These results support the concept that activation of serotonergic and noradrenergic bulbospinal neurons mediates SPA and additionally suggest that the noradrenergic component involves an alpha 2 noradrenergic receptor.

Preoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens.

BACKGROUND AND PURPOSE: Tumor progression is often difficult to distinguish from nonneoplastic treatment response on the basis of MR images alone. This study correlates metabolite levels measured by preoperative MR spectroscopic (MRS) imaging with histologic findings of biopsies, obtained during image-guided resections of brain mass lesions, to clarify the potential role of MRS in making this distinction. METHODS: Twenty-nine patients with brain tumors underwent high-resolution (0.2-1 cc) 3D proton MRS imaging and MR imaging before undergoing surgery; 11 had a newly diagnosed neoplasm, and 18 had recurrent disease. Surgical biopsies were obtained from locations referenced on MR images by guidance with a surgical navigation system. MR spectral voxels were retrospectively centered on each of 79 biopsy locations, and metabolite levels were correlated with histologic examination of each specimen. RESULTS: All mass lesions studied, whether attributable to tumor or noncancerous effects of previous therapy, showed abnormal MR spectra compared with normal parenchyma. When the pattern of MRS metabolites consisted of abnormally increased choline and decreased N-acetyl aspartate (NAA) resonances, histologic findings of the biopsy specimen invariably was positive for tumor. When choline and NAA resonances were below the normal range, histologic findings were variable, ranging from radiation necrosis, astrogliosis, and macrophage infiltration to mixed tissues that contained some low-, intermediate-, and high-grade tumor. CONCLUSION: This study demonstrated that 3D MRS imaging can identify regions of viable cancer, which may be valuable for guiding surgical biopsies and focal therapy. Regions manifesting abnormal MR spectra had a mixture of histologic findings, including astrogliosis, necrosis, and neoplasm.

Use of intrathecally administered morphine in the treatment of postoperative pain after lumbar spinal surgery: a prospective, double-blind, placebo-controlled study.

Improved control of postoperative pain is now known to reduce the incidence of morbidity. Although spinally administered narcotics have found a clear role in chest and abdominal surgery, their role in lumbar spinal surgery is debated. We conducted a prospective, double-blind, randomized, placebo-controlled trial of intrathecally administered morphine sulfate after lumbar spinal surgery in 56 patients. Patients received 0, 0.125, 0.25, or 0.5 mg of intrathecally administered morphine during extradural lumbar spinal operations, and the effects on postoperative analog pain scores, narcotic consumption, complications, and length of hospitalization were assessed. As compared with systemic narcotic administration, intrathecally administered morphine provided superior analgesia in a dose-dependent fashion without an increase in narcotic side effects. Consumption of parenteral narcotics on the first postoperative day and over the total hospitalization period decreased in correlation with increasing doses of intrathecally administered morphine. Mean length of hospitalization was significantly decreased, as compared with the control group, in patients receiving 0.25 or 0.5 mg of intrathecally administered morphine. When proper precautions are observed, intrathecally administered morphine can improve the postoperative care of patients undergoing lumbar spinal surgery.

Malignant optic glioma presenting radiologically as a "cystic" suprasellar mass: case report and review of the literature.

The diagnosis of malignant glioma of the optic nerves and chiasm may be difficult because these rare lesions may mimic other suprasellar lesions. We report a case of glioblastoma multiforme of the optic chiasm in which the appearance of the lesion on computed tomographic (CT) scan was consistent with that of craniopharyngioma or cystic pituitary adenoma. We suggest that malignant optic glioma should be considered in the differential diagnosis of an adult with progressive visual loss of rapid onset, even when ophthalmological examination strongly suggests extrinsic compression of the anterior optic pathways and when the CT scan apparently indicates a cystic mass lesion.