Pitfalls and uncertain prognosis in pathological diagnosis of psammomatous melanotic schwannoma

A 20-year-old woman presenting with a pelvic mass identified as a psammomatous melanotic schwannoma (PMS) with atypical histological features was later found to have family history of cardiac myxomas consistent with Carney’s complex. The BRAF V600E mutation was absent in the tumor.     

Differential diagnosis between melanotic schwannoma of gasserian ganglion and metastatic melanoma of middle cranial fossa

We present a case of a rare tumor--melanotic schwannoma of trigeminal nerve root and gasserian ganglion. Differential diagnosis between metastatic melanoma and melanotic schwannoma (MS) is associated with serious difficulties and high responsibility. Metastatic melanoma is a high grade tumor while most MS are benign lesions with good outcome. By the date 105 cases of these tumors are described in the world literature, 3 of them originated from trigeminal nerve root and gasserian ganglion. MS predominantly occur in relatively young patients, they are characterized by presence of Carney's complex and psammomatous bodies and absence of primary focus. MS and metastatic melanoma have similar appearance on MRI due to presence of melanin granules. Indirect signs evident for MS include cystic structure and dumbbell-shaped growth. Metastatic melanoma of cranial nerves is more typical in people older than 40, primary focus in the face in the zone of innervation of affected nerve is common. In case of absence of the listed features differential diagnosis is based on immunohistochemical analysis and electron microscopy of tissue samples.     

Auditory cortex lesions and discrimination of spatial location by the rat

Five normal rats and four rats with bilateral lesions of auditory cortex were tested by the conditioned suppression procedure to determine their abilities to discriminate between spatially separated sound sources. The discrimination involved detection of a change in location of a train of clicks from a speaker on the animals' left to a speaker on the right. The separation between speakers was varied from 180° to 90°, 45°, 22°, 12°, 6°, and psychophysical functions were obtained using a method of descending limits. Both normal and brain-damaged animals were capable of discriminating left from right clicks and psychophysical curves were similar for the two groups. Histological analysis indicated that the lesions in each of the four brain-damaged rats destroyed primary auditory cortex as well as surrounding belt areas. Therefore, for the rat, auditory cortex was not found to be essential for discrimination of the spatial locations of auditory stimuli. The results are discussed in light of impairments in sound localization following lesions of auditory cortex in other mammalian species.     

Dorsolateral prefrontal cortex lesions and discrimination of movement-produced cues by rhesus monkeys

Rhesus monkeys were trained on a conditional discrimination in which sequences of either 32 or 64 lever presses served as discriminative stimuli. For half the subjects, reinforcement was contingent upon choice of a red response key following a sequence of 32 presses (FR 32), and a white key after FR 64, with the position of the two key colors randomized across trials. The remaining subjects were reinforced for left key presses after FR 64, and right key presses after FR 32, with key color again randomized across trials. Ablation of dorsolateral prefrontal cortex resulted in postoperative deficits in all subjects, although 6 of 8 eventually remastered the task. This recovery was investigated in a second experiment, in which psychophysical functions were generated by varying the length of the shorter FR. Although dorsolateral lesions again produced a severe disruption in performance, the post-operative functions eventually obtained were identical to the preoperative functions. This pattern of marked impairment in retention of fixed ratio discriminations, but no change in asymptotic capacity, suggests participation of dorsolateral prefrontal cortex in processing kinesthetic information, possibly analogous to the role of inferior temporal cortex in processing visual information.     

GNA11 and N‐RAS mutations: alternatives for MAPK pathway activating GNAQ mutations in primary melanocytic tumours of the central nervous system

M. Gessi, J. Hammes, L. Lauriola, E. Dörner, J. Kirfel, G. Kristiansen, A. zur Muehlen, D. Denkhaus, A. Waha and T. Pietsch (2013) Neuropathology and Applied Neurobiology 39, 417–425 GNA11 and N‐RAS mutations: alternatives for MAPK pathway activating GNAQ mutations in primary melanocytic tumours of the central nervous system Aim: Primary melanocytic tumours are uncommon neoplasms of the central nervous system. Although similarities with uveal melanomas have been hypothesized, data on their molecular features are limited. Methods: In this study, we investigated the mutational status of BRAF^V600E, KIT, GNAQ, GNA11, N‐RAS and H‐RAS in a series of 19 primary melanocytic tumours of the central nervous system (CNS). Results: We identified six cases harbouring mutations in the hotspot codon 209 of the GNAQ gene and two cases with mutations in the hotspot codon 209 of the GNA11 gene. Two mutations in codon 61 of N‐RAS were also found. In the single strand conformation polymorphism (SSCP) analysis, no shifts corresponding to BRAF^V600E mutations or suggesting activating mutations in the KIT gene were observed. Conclusions: In primary melanocytic tumours of the CNS, GNA11 and N‐RAS mutations represent a mechanism of MAPK pathway activation alternative to the common GNAQ mutations. On the other hand, BRAF^V600E mutations and activating KIT mutations seem to be absent or very rare in these tumours.     

Automated morphological analysis by means of dynamic time-warping

A new technique for the clustering of EEG wave forms is proposed. This method, termed dynamic time-warping (DTW) based clustering, involves the determination of a distance measure by allowing a certain degree of flexibility in the time axes of the two waves to be compared. Sharp waves and spikes, taken from actual EEG data, were subjected to the DTW-clustering approach. The results were compared with an approach based on features extracted from the wave forms and one based on computing the peak-aligned difference between wave forms. It was found that the DTW approach resulted in more homogeneous clusters than the other two approaches. These results, although preliminary, clearly indicate the feasibility of applying this new method for wave form clustering.     

The effects of posterior cortical lesions on eye orientation during visual discrimination by monkeys

Motion pictures were taken of the eyes of monkeys as they learned two-choice visual discriminations. Preoperative gaze patterns were compared to gaze patterns following ablation of visual areas in the temporal and occipital lobes. After inferotemporal and prestriate lesions, monkeys showed increased postoperative staring at the discriminanda on the preferred side, decreased rate of gaze shift from one stimulus to another and, as expected, slower learning.     

Visual discrimination between spatially separated stimuli by cats with lesions of the superior colliculus-pretectum

(1) This study was designed to test the ability of cats with lesions of the superior colliculus-pretectum to discriminate between stimuli which are widely separated in space. (2) Intact cats and cats learning or relearning after lesions of the superior colliculus-pretectum, were trained on light-dark (LD) and horizontal-vertical stripe (HV) discriminations in a V-maze, where the stimuli were widely separated in space, or in a divided straight maze, where the stimuli were side by side. (3) Two types of errors were scored: door-push errors when the cat pushed open the incorrect door; alley-entrance errors when the cat entered the incorrect alley, but turned and entered the correct alley without having pushed the incorrect door. (4) In the V-maze as well as in the straight maze, cats with lesions of the superior colliculus-pretectum achieved criterional performance by alley-entrance and door-push scoring on LD and HV discriminations. Thus, cats with lesions of the superior colliculus-pretectum can locate or orient to widely separated visual stimuli well enough to discriminate between them from a distant choicepoint. (5) Cats with lesions of the superior colliculus-pretectum generally committed a larger number and higher percentage of alley-entrance errors during learning than unoperated cats in either maze. However, commission of alley-entrance errors was not further increased in the V-maze, where the stimuli were widely separated in space. (6) All unoperated cats committed alley-entrance errors as well as door-push errors suggesting that commission of alley-entrance errors may reflect a normal process in two-choice learning.     

Effects of combined serotonin depletion and lesions of the nucleus basalis magnocellularis on acquisition of a complex spatial discrimination task in the rat

The purpose of the present experiment was to determine the effects of lesions of cholinergic neurons originating from the nucleus basalis magnocellularis (NBM), alone or in combination with central serotonin depletion, on learning and memory in rats trained in the Stone 14-unit T-maze--a complex, positively-reinforced spatial discrimination task. Lesion of cholinergic neurons within the NBM was accomplished by bilateral infusion of ibotenic acid. Serotonin depletion was accomplished by the systemic administration of p-chloroamphetamine (PCA). The results show that PCA-induced serotonin depletion enhanced learning. This effect was completely prevented by NBM lesions, despite the fact that NBM lesions alone did not affect the performance of rats in this task. The results of this study support the view that the cholinergic and serotonergic systems may functionally interact in learning and memory processes. The significance of this interaction in the etiology and treatment of dementia should be further investigated.     

Visual intensity and pattern discrimination deficits after lesions of ectostriatum in pigeons

Eighteen pigeons were trained to discriminate between visual stimuli that differed in either intensity or pattern. Bilateral, electrolytic lesions were made in ectostriatum or the lateral neostriatum. Pigeons with ectostriatum lesions had severe post-operative performance deficits. The magnitude of the deficit and the amount of post-operative retraining necessary to restore the birds to pre-operative performance levels varied directly with the amount of bilateral destruction of ectostriatum. Pigeons with little or no involvement of ectostriatum showed little or no change in discrimination performance post-operatively. Similarities between morphological and functional organization of the reptilian, avian and mammalian visual systems are discussed.     

Effects of partial hippocampal lesions by ibotenic acid on repeated acquisition of spatial discrimination in pigeons

Pigeons were trained on a spatial discrimination task using a repeated acquisition procedure. In this procedure, the pigeons were trained to discriminate between the positions of three keys. One of them was designated the correct key. When the subjects reached the criterion, the discrimination task was changed, with one of two previously incorrect keys now being made the correct key. This procedure was repeated at least 15 times. Then, lesions to the whole hippocampus, the medial hippocampus or to the lateral hippocampus were made by injections of ibotenic acid (Experiment 1). Only the subjects with damage to the whole hippocampus showed deficits in learning after the lesions. The deficits were similar to those caused by aspiration lesions /37/. Knife cuts separating the medial and lateral hippocampi were made in Experiment 2. The subjects did not show deficits in the spatial discrimination task after the sections. Although studies of the connectivity in the avian hippocampus suggested functional differences between the medial and lateral hippocampi, the present results show that pigeons can learn spatial discrimination with the medial and lateral parts of hippocampus separated.     

Linkage and mutational analysis of CLCN2 in childhood absence epilepsy

In order to assess the chloride channel gene CLCN2 as a candidate susceptibility gene for childhood absence epilepsy, parametric and non-parametric linkage analysis was performed in 65 nuclear pedigrees. This provided suggestive evidence for linkage with heterogeneity: NPL score=2.3, p<0.009; HLOD=1.5, alpha=0.44. Mutational analysis of the entire genomic sequence of CLCN2 was performed in 24 unrelated patients from pedigrees consistent with linkage, identifying 45 sequence variants including the known non-synonymous polymorphism rs2228292 (G2154C, Glu718Asp) and a novel variant IVS4+12G>A. Intra-familial association analysis using the pedigrees and a further 308 parent-child trios showed suggestive evidence for transmission disequilibrium of the G2154C minor allele: AVE-PDT chi(1)2 = 5.17, p<0.03. Case-control analysis provided evidence for a protective effect of the IVS4+12G>A minor allele: chi(1)2 = 7.27, p<0.008. The 65 nuclear pedigrees were screened for three previously identified mutations shown to segregate with a variety of idiopathic generalised epilepsy phenotypes (597insG, IVS2-14del11 and G2144A) but none were found. We conclude that CLCN2 may be a susceptibility locus in a subset of cases of childhood absence epilepsy.     

Impairments in visual discrimination learning and recognition memory produced by neurotoxic lesions of rhinal cortex in rhesus monkeys

Much work on the cognitive functions of the primate rhinal (i.e. entorhinal plus perirhinal) cortex has been based on aspiration lesions of this structure, which might disrupt fibres passing nearby and through the rhinal cortex in addition to removing the cell bodies of the rhinal cortex itself. To determine whether damage limited to the cell bodies of the rhinal cortex is sufficient to impair visual learning and memory, four rhesus monkeys (Macaca mulatta) were preoperatively trained on a battery of visual learning and memory tasks, including single-pair discrimination learning for primary reinforcement, single-pair discrimination reversals, concurrent discrimination learning and reversal, and delayed matching-to-sample. Following acquisition of these tasks and a preoperative performance test, ibotenic acid was injected bilaterally into the rhinal cortex, and the monkeys were retested. Consistent with the results of studies using aspiration lesions, the monkeys were impaired on single-pair discrimination learning as well as recognition memory performance postoperatively, although reliable reversal learning impairments were not observed. The magnitude of postoperative impairment in discrimination learning was not correlated with the magnitude of postoperative impairment in recognition memory, suggesting a possible dissociation between these functions within the rhinal cortex. The correspondence of behavioural deficits following aspiration and neurotoxic lesions of the rhinal cortex validates the attribution of various cognitive functions to this structure, based on the results of studies with aspiration lesions.