Subacute cognitive disorders as initial presentation of intravascular lymphoma: a case report and review of literature

Intravascular lymphoma is a rare subtype of diffuse large B cell lymphoma, characterized by proliferation of mature B cells within the lumina of small and medium vessels of many organs, without parenchymal involvement. The clinical phenotype is extremely variegated; moreover, neurological symptoms such as encephalopathy and focal neurological deficits occur and often coincide with disease’s debut. We described the clinical course of a patient with intravascular diffuse large B cell lymphoma presented with subacute cognitive decline without focal signs, later associated to aspecific general symptoms that rapidly evolved to a severe inexplicable encephalopathy accompanied to systemic failure.     

Intrathecal substance P-induced thermal hyperalgesia and spinal release of prostaglandin E2 and amino acids

Substance P is an important neuromediator in spinal synaptic transmission, particularly in processing nociceptive afferent information. The effects of substance P are mediated by activation of the neurokinin 1 receptor. Evidence has suggested that excitatory amino acids such as glutamate, and prostaglandins including prostaglandin E2 are involved in the enhanced spinal excitability and hyperalgesia produced by spinal substance P. In the present study, we have demonstrated that intrathecal injection of substance P (20 nmol) in rats chronically implanted with intrathecal dialysis catheters induced a decrease in thermal paw withdrawal latency (before: 10.4+/-0.3 s; after 7.6+/-0.6 s), which was accompanied by an increase in prostaglandin E2 (362+/-37% of baseline), glutamate (267+/-84%) and taurine (279+/-57%), but not glycine, glutamine, serine or asparagine. Intrathecal injection of artificial cerebrospinal fluid had no effect upon the behavior or release. Substance P-induced thermal hyperalgesia and prostaglandin E2 release were significantly attenuated by a selective neurokinin 1 receptor antagonist RP67580, but not by an enantiomer RP68651. However, substance P-induced release of glutamate and taurine was not reduced by treatment with RP67580. SR140333, another neurokinin 1 receptor antagonist, displayed the same effects as RP67580 (i.e. block of thermal hyperalgesia and prostaglandin E2 release, but not release of amino acids). These results provide direct evidence suggesting that the spinal substance P-induced thermal hyperalgesia is mediated by an increase in spinal prostaglandin E2 via activation of the neurokinin 1 receptor. These findings define an important linkage between small afferents, sensory neurotransmitter release and spinal prostanoids in the cascade of spinally-mediated hyperalgesia. The evoked release of glutamate is apparently not a result of activation of neurokinin 1 receptors. Accordingly, consistent with other pharmacological data, acute spinal glutamate release does not contribute to the hyperalgesia induced by activation of spinal neurokinin 1 receptors.     

Segmental and laminar distributions of nicotinamide adenine dinucleotide phosphate-diaphorase-expressing and neuronal nitric oxide synthase-immunoreactive neurons versus radioassay detection of catalytic nitric oxide synthase activity in the rabbit spinal cord

The distributions of neuronal nitric oxide synthase-immunoreactive neurons and of nicotinamide adenine dinucleotide phosphate-diaphorase activity were studied in the C6, Th2, L1, L5, S2 and S3 segments and laminae in the rabbit spinal cord and compared with the catalytic nitric oxide synthase activity, determined by monitoring the conversion of [3H]arginine to [3H]citrulline in the same segments and laminae. Morphologically, a heterogeneous population of nicotinamide adenine dinucleotide phosphate-diaphorase-expressing and neuronal nitric oxide synthase-immunoreactive neurons was detected in the superficial and deep dorsal horn and the pericentral region in all segments studied, and in the intermediolateral cell column of the thoracic and lumbosacral segments. A disproportionate distribution of both neuronal categories which had a significantly higher number of nicotinamide adenine dinucleotide phosphate-diaphorase-expressing rather than neuronal nitric oxide synthase-immunoreactive cell bodies was found in all segments. The catalytic nitric oxide synthase activity was distributed unequally in the C6, Th2, L1, L5, S2 and S3 segments, with a comparatively low value in the Th2 segment (70 +/- 5.1 d.p.m./microg protein) in comparison with the S3 segment, where the highest level (140 +/- 5.5 d.p.m./microg protein) was found. A close correlation between the number of neuronal nitric oxide synthase-immunoreactive somata and catalytic nitric oxide synthase activity was revealed in the dorsal horn (laminae I-VI). Whereas a low number of neuronal nitric oxide synthase-immunoreactive somata in laminae VII-X was found in the L5, S2 and S3 segments, the values of catalytic nitric oxide synthase activity in the same laminae and segments were found to be exceedingly high. These findings indicate that the occurrence of many neuronal nitric oxide synthase-immunoreactive fibers (mainly axons), and dense, punctate, non-somatic neuronal nitric oxide synthase immunopositivity in the neuropil staining of the same laminae and segments, can substantially enhance catalytic nitric oxide synthase activity.     

Localization of NADPHd-exhibiting neurons in the spinal cord of the rabbit

Segmental and laminar distributions of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-exhibiting neurons were examined in the rabbit spinal cord by using horizontal, sagittal, and transverse sections. A large number of NADPHd-positive neurons in the spinal cord of rabbit appeared to fall into six categories (N1-N6), but others could not be classified. Major cell groups of NADPHd-exhibiting neurons were identified in the superficial dorsal horn and around the central canal at all spinal levels and in the intermediolateral cell column at thoracic and upper lumbar levels. NADPHd-exhibiting neurons of the pericentral region were divided into a thin subependymal cell column containing longitudinally arranged, small bipolar neurons with processes penetrating deeply into the intermediolateral cell column and/or running rostrocaudally in the subependymal layer. The second pericentral cell column located more laterally in lamina X contains large, intensely stained NADPHd-exhibiting neurons with long dendrites radiating in the transverse plane. In the pericentral region (lamina X), close association of NADPHd-exhibiting somata and fibers and mostly longitudinally oriented blood vessels were detected. Neurons of the sacral parasympathetic nucleus, seen in segments S1-S3, exhibited prominent NADPHd cellular staining accompanied by heavily stained fibers extending from Lissauer's tract through lamina I along the lateral edge of the dorsal horn to lamina V. A massive dorsal gray commissure, highly positive in NADPHd staining, was found in segments S1-S3. Scattered positive cells were also found in the deeper dorsal horn, ventral horn, and white matter. Fiberlike NADPHd staining was found in the superficial dorsal horn and pericentral region in all the segments studied. Dense, punctate, nonsomatic NADPHd staining was detected in the superficial dorsal horn, in the pericentral region all along the rostrocaudal axis, and in the nucleus phrenicus (segments C4-C5), nucleus dorsalis (segments Th2-L2), Onuf's nucleus (segments S1-S3), and the dorsal part of the dorsal gray commissure (S1-S3).     

The regional distribution of nitric oxide synthase activity in the spinal cord of the dog

The aim of this study was to examine the distribution of calcium-dependent nitric oxide synthase activity (cNOS) in the white and gray matter in cervical, thoracic, lumbar and sacral segments of the spinal cord and cauda equina of the dog. The enzyme's activity, measured by the conversion of [3H]arginine to [3H]citrulline revealed considerable region-dependent differences along the rostrocaudal axis of the spinal cord in general and in cervical (C1, C2, C4, C6 and C8) and lumbar (L1-L3, L4-L7) segments in particular. In the non-compartmentalized spinal cord, the cNOS activity was lowest in the thoracic and highest in the sacral segments. No significant differences were noted in the gray matter regions (dorsal horn, intermediate zone and ventral horn) and the white matter columns (dorsal, lateral and ventral) in the upper cervical segments (C1-C4), except for a significant increase in the ventral horn of C4 segment. In C6 segment, the enzyme's activity displayed significant differences in the intermediate zone, ventral and lateral columns. Surprisingly, extremely high cNOS activity was noted in the dorsal horn and dorsal column of the lowest cervical segment. Comparing the enzyme's activity in upper and lower lumbar segments of the spinal cord, cNOS activity prevailed in L4-L7 segments in the dorsal horn and in all the above mentioned white matter columns.     

The case for the bulbospinal respiratory nitric oxide synthase-immunoreactive pathway in the dog

Previous investigations from our laboratory have documented that the neuropil of the phrenic nucleus contains a dense accumulation of punctate nicotinamide adenine dinucleotide phosphate diaphorase staining. In this study we investigated the occurrence and origin of punctate nitric oxide synthase immunoreactivity in the neuropil of the phrenic nucleus in C3-C5 segments, supposed to be the terminal field of the premotor bulbospinal respiratory nitric oxide synthase-immunoreactive pathway in the dog. As the first step, nitric oxide synthase immunohistochemistry was used to characterize nitric oxide synthase-immunoreactive staining of the phrenic nucleus and nitric oxide synthase-containing neurons in the dorsal and rostral ventral respiratory group and in the B?tzinger complex of the medulla. Dense punctate nitric oxide synthase immunoreactivity was found on control sections in the neuropil of the phrenic nucleus. Several thin bundles of nitric oxide synthase-immunoreactive fibers were found to enter the phrenic nucleus from the lateral and ventral column. Nitric oxide synthase-containing neurons were revealed in the dorsal respiratory group of medulla corresponding to the ventrolateral nucleus of the solitary tract and in the rostral ventral respiratory group beginning approximately 1 mm caudal to the obex and reaching to 650 microm rostral to the obex. Axotomy-induced retrograde changes, consisting in a strong upregulation of nitric oxide synthase-containing neurons, were found in the dorsal and rostral ventral respiratory group contralateral to the hemisection performed at the C2-C3 level. Concurrently, a strong depletion of the punctate nitric oxide synthase immunopositivity in the neuropil of the phrenic nucleus ipsilaterally with the hemisection was detected, thus revealing that a crossed premotor bulbospinal respiratory pathway contains a fairly high number of nitric oxide synthase-immunopositive fibers terminating in the phrenic nucleus. The use of the retrograde fluorescent tracer Fluorogold injected into the phrenic nucleus and an analysis of sections cut through the dorsal and rostral ventral respiratory group and B?tzinger complex of medulla and processed for nitric oxide synthase immunocytochemistry revealed that approximately 73.8% of crossed premotor bulbospinal respiratory nitric oxide synthase-immunoreactive axons originate in the rostral ventral respiratory group and 26.2% is given by nitric oxide synthase-containing neurons of the dorsal respiratory group. A few premotor nitric oxide synthase-immunoreactive axons originating from the B?tzinger complex were found. In summary, the present study provides evidence for a hitherto unknown premotor bulbospinal respiratory nitric oxide synthase-immunoreactive pathway connecting the bulbar respiratory centers with the motor neurons of the phrenic nucleus in the dog.     

Axoplasmic transport of monoamine oxidase after ischemia

Rabbit spinal cords were subjected to 40 min of ischemia by abdominal aorta occlusion followed by 1 or 4 days of recirculation. Axoplasmic transport of mitochondria was investigated by monitoring the accumulation of monoamine oxidase activity (MAO, EC 1.4.3.4) at the proximal and distal ligatures placed on sciatic nerves. Within 1 day following ischemia, MAO accumulation was reduced to 45% and 34% at the proximal and distal ties, respectively. Within 4 days after ischemia, MAO accumulation was depressed still further to 22% in either direction. The substantial decrease in transport velocity appears to be the immediate cause for the observed decrease in MAO accumulation in sciatic nerve.