Dynorphinergic system alterations in the corticostriatal circuitry of neuropathic mice support its role in the negative affective component of pain.

The dynorphinergic system is involved in pain transmission at spinal level, where dynorphin exerts antinociceptive or pronociceptive effects, based on its opioid or non-opioid actions. Surprisingly, little evidence is currently available concerning the supraspinal role of the dynorphinergic system in pain conditions. The present study aimed to investigate whether neuropathic pain is accompanied by prodynorphin (Pdyn) and κ-opioid receptor (Oprk1) gene expression alterations in selected mouse brain areas. To this end, mice were subjected to chronic constriction injury of the right sciatic nerve and neuropathic pain behavioral signs were ascertained after 14 days. At this interval, a marked increase in Pdyn mRNA in the anterior cingulate cortex (ACC) and prefrontal cortex (PFC) was observed. Oprk1 gene expression was increased in the PFC, and decreased in the ACC and nucleus accumbens (NAc). No changes were observed in the other investigated regions. Because of the relationship between dynorphin and the brain-derived neurotrophic factor, and the role of this neurotrophin in chronic pain-related neuroplasticity, we investigated brain-derived neurotrophic factor gene (Bdnf) expression in the areas showing Pdyn or Oprk1 mRNAs changes. Bdnf mRNA levels were increased in both the ACC and PFC, whereas no changes were assessed in the NAc. Present data indicate that the dynorphinergic system undergoes quite selective alterations involving the corticostriatal circuitry during neuropathic pain, suggesting a contribution to the negative affective component of pain. Moreover, parallel increases in Pdyn and Bdnf mRNA at cortical level suggest the occurrence of likely interactions between these systems in neuropathic pain maladaptive neuroplasticity.

N/OFQ system in brain areas of nerve-injured mice: its role in different aspects of neuropathic pain.

Several studies showed that chronic pain causes reorganization and functional alterations of supraspinal brain regions. The nociceptin-NOP receptor system is one of the major systems involved in pain control and much evidence also suggested its implication in stress, anxiety and depression. Therefore, we investigated the nociceptin-NOP system alterations in selected brain regions in a neuropathic pain murine model. Fourteen days after the common sciatic nerve ligature, polymerase chain reaction (PCR) analysis indicated a significant decrease of pronociceptin and NOP receptor mRNA levels in the thalamus; these alterations could contribute to the decrease of the thalamic inhibitory function reported in neuropathic pain condition. Nociceptin peptide and NOP mRNA increased in the anterior cingulate cortex (ACC) and not in the somatosensory cortex, suggesting a peculiar involvement of this system in pain regulating circuitry. Similarly to the ACC, an increase of nociceptin peptide levels was observed in the amygdala. Finally, the pronociceptin and NOP mRNAs decrease observed in the hypothalamus reflects the lack of hypothalamus-pituitary-adrenal axis activation, already reported in neuropathic pain models. Our data indicate that neuropathic pain conditions affect the supraspinal nociceptin-NOP system which is also altered in regions known to play a role in emotional aspects of pain.

Effects of acute ethanol exposure on class I HDACs family enzymes in wild-type and BDNF(+/-) mice.

BACKGROUND: Alterations of brain-derived neurotrophic factor (BDNF) have been associated with the development of addiction to different drugs of abuse, including ethanol (EtOH). EtOH exposure activates the BDNF-signaling cascade in dorsal striatum, which in turn affects further EtOH intake. Different alcohol exposures have been widely demonstrated to modulate chromatin remodeling, affecting histone acetylation/deacetylation balance. Recently, class I histone deacetylases (HDACs) inhibition has been reported to modulate BDNF mRNA expression and to attenuate morphological and behavioral phenomena related to EtOH exposure. However, the role played by different HDAC isoforms in EtOH-induced plasticity is still unclear. METHODS: We investigated the effects induced by acute EtOH exposure on the protein levels of class I HDAC 1-3 isoforms of wild-type (WT) and BDNF heterozygous mice (BDNF(+/-)), in nuclear and cytoplasmic extracts of specific brain regions associated with EtOH addiction. RESULTS: Nuclear HDAC 1-3 levels were markedly reduced after acute EtOH treatment in the caudate putamen (CPu) of WT mice only. Furthermore, CPu basal levels of nuclear HDAC isoforms were significantly lower in BDNF(+/-) mice compared to WT. With the exception of nuclear HDAC 3, no significant changes were observed after acute EtOH treatment in the prefrontal cortex (PFCx) of BDNF(+/-) and WT mice. In this area, the nuclear HDAC basal levels were significantly different between the two experimental groups. CONCLUSIONS: These results provide details about EtOH effects on class I HDAC isoforms and strongly support a correlation between BDNF and class I HDACs, suggesting a possible influence of BNDF on these enzymes.

Diaphragma sellae meningiomas. Report of two cases and a review of the literature.

Diaphragma sellae meningiomas are very rare and often manifest themselves with aspecific symptoms. Before the advent of MR, the diagnosis was very difficult or even impossible. For this reason they were often included in the broader category of suprasellar meningiomas. We describe two cases of diaphragma sellae meningiomas anterior to the pituitary stalk, manifesting with visual disturbances. We present the clinic and diagnostic data and we compare our experience with that reported in the literature. The tumor were removed by pterional (case 1) and subfrontal approach (case 2) with a recover of vision. Our experience support a clear demarcation of the diaphragma sellae meningioma among the wither group of suprasellar meningiomas. It is mandatory to define its position relative to the pituitary stalk and to the diaphragma sellae to chose the best surgical approach.

Acute subdural hematoma and pachymeningitis carcinomatosa: case report.

Subdural hematomas may affect 0.4-5 p. 100 of patients with cancer, because of predisposing risk factors or because of the cancer itself. The most likely association is with hematological cancer with coagulative disorders. An association with pachymeningitis carcinomatosa is less likely. In this instance the subdural hematoma is due to a neoplastic obstruction of dural vein with subdural engorgement and hemorrhage or subdural effusion. We report a case in which an acute neurological deterioration due to a subdural hematoma disclosed a dural metastasis from a breast cancer operated four years earlier and present a literature review.

Neuroma of the spinal accessory nerve disclosed by a subarachnoid hemorrhage: case report.

OBJECTIVE AND IMPORTANCE: Neuroma of the 11th nerve disclosed by subarachnoid bleeding is a very rare condition. Clinical diagnosis is almost impossible, but previous episodes of muscle spasm and mild signs of subarachnoid hemorrhage with a hematoma in the cisterna magna should suggest magnetic resonance imaging as well as angiography. CLINICAL PRESENTATION: We present a case of an 11th nerve neuroma disclosed by subarachnoid bleeding. Previous episodes of muscle spasm and neck pain treated with nonsteroid anti-inflammatory drugs had been overlooked, preventing the neuroma from being diagnosed at that time. The computed tomographic scan showed an intracisternal hematoma spreading into the subarachnoid space. The hematoma appeared heterogeneous on the magnetic resonance image, and a tumor mass growing into the cisterna magna against the brain stem was also revealed. INTERVENTION: The tumor was totally removed by a suboccipital craniectomy and C1 laminectomy. It originated from the spinal root of the 11th nerve, from which it was able to be dissected without damage to the nerve. CONCLUSION: To our knowledge, this is the first reported case of an 11th nerve neuroma disclosed by a subarachnoid hemorrhage. Furthermore, this is the seventh documented case of an 11th nerve neuroma developing in the cisterna magna. We emphasize the importance of a high index of suspicion for the rare instances of hematic density limited to the cisterna magna, especially if associated with recurring episodes of localized neck pain and muscle spasm treated with nonsteroid anti-inflammatory drugs.

Inter-hemispheric scissure, a rare location for a traumatic subdural hematoma, case report and review of the literature.

Subdural interhemispheric hematomas (ISH), though not really rare, are quite an uncommon complication of head traumas. This condition is more frequent in childhood, where it is generally considered as a part of a more complex syndrome, called 'Shaken Children Syndrome', usually pointing out child abuse. Although a head injury is very often considered the cause (in about 80-90% of the cases), possible predisposing factors such as coagulopathies, alcohol abuse or anticoagulant therapy can also be considered. Furthermore, as the rupture of an intracranial aneurysm has also occasionally pinpointed as a possible cause, this event should be kept in mind in order to be able to address exactly both the diagnostic and therapeutical procedures. A new conservatively managed case is thereby described. A review of the literature with particular attention drawn to the diagnosis and the different therapeutical possibilities is also elaborated.

Ischemic stroke syndromes in childhood.

The ischemic stroke syndrome is very broad and encompasses a wide range of underlying conditions. Its identification is of great importance in clinical routine, in particular in the management of young patients who have acute neurologic deficits. The introduction of CT, MR and ultra-sound demonstrating lesions of the brain and in certain degree of the cerebral arteries has in general eliminated the need for angiography as a first examination. The most common underlying anomaly found with thrombotic or embolic stroke is congenital or acquired heart disease. Thus, it is essential that patients with cerebral ischemia be submitted to a complete cardiac examination. Children tend to show more recovery after a stroke than adults do.

Waldenström's macroglobulinemia associated with glioblastoma. A case report.

Waldenström Macroglobulinemia (WM) involves the Central Nervous System in about 10% of the affected patients, but only occasionally related clinical and histopathological changes have been considered. Most of the published papers focus on leptomeningeal lymphoplasmacytic infiltrates, even though the damage to the CNS results in a more variegated scenario. Association to a malignant neoplasm, usually of lymphoid series, is not uncommon, instead association with a glioblastoma is rare, and only 3 cases have been reported. Despite the rarity of this finding, the association Waldenström Macroglobulinemia-glioblastoma may not be coincidental. Probable etiopathological links are thereby discussed.

Luigi Rolando and his pioneering efforts to relate structure to function in the nervous system.

The fissure separating the motor from the sensory cortex and the substantia gelatinosa capping the posterior horn of the spinal cord are still known by the name of the Italian anatomist Rolando, Luigi Rolando was born in Turin, Italy, in 1773 and died in 1831. His life was not easy, the first of his problems being the death of his father when Rolando was still very young. Three people were to be influential in his life and career: Father Maffei, his maternal uncle who raised him; Dr. Cigna, the anatomy professor who discovered his talent; and Dr. Anformi, a general practitioner who introduced him to the practice of medicine and to the best circles of the city. Forced to leave Turin by the Napoleonic invasion of the country, Rolando first stopped in Florence, where he learned about anatomical dissection, drawing, and engraving and studied the appearance of nervous tissue under the microscope. Later he went to Sardinia where, although cut off from European cultural circles, he developed his major theories. Rolando pioneered the idea that brain functions could be differentiated and located in specific areas and discovered the fixed pattern of cerebral convolutions, highlighting motor and sensory gyri. He demonstrated the complexity of the central gray matter of the spinal cord, describing the "substantia gelatinosa," and he deduced that nervous structures are connected in a network of nervous fibers linked by electrical impulses. Rolando had to struggle for recognition, however, as the priority of his discoveries was challenged by the almost contemporaneous work of Gall and Spurzheim on cerebral localization and of Flourens on cerebellar function. Nevertheless, his efforts contributed greatly to the clarification of brain function. His observations on nervous anatomy have been especially accurate, as shown by the nomenclature "fissure of Rolando."

Analysis of static and kinetic abnormalities typical of torticollis, and postoperative changes.

The clinical pattern of torticollis and surgical results were evaluated. Head posture and range of motion were measured. The authors use a newly designed device consisting of an orthogonal system to which head position is referred. Preliminary data were obtained on 24 patients with torticollis and 21 healthy control subjects. The examination of posture shows that the head usually twists in opposite directions simultaneously around a vertical and a sagittal axis, and the deflection is greater in one direction. Head position affect body posture, with the trunk often compensating for head deviation. Although there are almost always abnormalities on EMG recordings of neck muscles, these do not indicate the degree and pattern of deformity. Because of the disorder of muscle innervation, head movements are affected, with an asymmetrical decrease in the range of motion in comparison with normals (p < 0.05). Movements are greater toward the direction of postural deviation. Eleven patients were studied before and after undergoing a bilateral C1-C3 rhizotomy and selective section of the XIth rootlets, which carry motor fibers to the sternocleidomastoid muscle. Head posture immediately improved (p < 0.05), with better appearance, despite some residual distortion (less than 10%), and trunk alignment also improved . In contrast to posture, head range of motion was worse than before (p < 0.05). The most improved movement was rotation, followed by flexion/extension. Further improvements were observed at later follow-up. Surprisingly, the range of motion gradually increased, surpassing preoperative limits (p < 0.05). Our study documents the usefulness of surgery in correcting torticollis. Posture is immediately affected; motion increases despite denervation, after an initial decline.

Treatment of spasmodic torticollis with intradural selective rhizotomies.

To determine the effects of ventral cervical and selective spinal accessory nerve rhizotomy on spasmodic torticollis, 58 patients who had undergone surgery between 1979 and 1987 were reviewed retrospectively. At the time of surgery, each nerve rootlet was electrically stimulated to determine its effect on the nuchal musculature prior to sectioning. Forty-nine patients (85%) had a marked improvement in their condition, with 33 (57%) attaining an excellent result and 16 (28%) noting significant improvement. Patients complained of abnormal head posture, nuchal muscle spasms, and pain prior to surgery. Muscle spasms were completely relieved in 42 patients (72%) and markedly reduced in 10 (17%). Of the 47 patients with preoperative pain, 30 (64%) were free of their pain and eight (17%) noted that the pain was reduced in intensity and frequency. Thirty-four patients (59%) reported that their resting head posture was restored to a neutral position. The likelihood that a patient's head posture returned to normal was inversely proportional to the preoperative duration of the spasmodic torticollis. Twenty-six patients (45%) suffered mild transient difficulty with swallowing solid foods in the immediate postoperative period. In most cases these minor difficulties abated in the months following surgery.

Accuracy of the analysis of multiple small fragments of glial tumors obtained by stereotactic biopsy.

To examine the reliability of the diagnoses reached on multiple small fragments of cerebral glial tumors obtained via stereotactic biopsy, samples obtained from 100 consecutive glial tumors (during real or simulated biopsy) were studied by cytology and histology. In comparison to the definitive diagnosis made on the whole tumor, a correct positive diagnosis on the biopsy sample was made by histology in 96% of cases and by cytology in 93% of the cases (with 96% correct results when combining both methods). A correct identification of the tumor type and grade was achieved by histology in 82% of cases and by cytology in 80% of the cases (with 85% correct results when combining both methods). The limits of stereotactic biopsy are related to the difficulty of identifying all of the typical tumor features on tiny tissue fragments of a pleomorphic neoplasm, such as a glioma. This study demonstrates that better results may be obtained by using both cytology and histology to study multiple stereotactic biopsy samples from glial tumors.

Management of primary or recurring grossly cystic craniopharyngiomas by means of draining systems. Topic review and 6 case reports.

In primary or relapsing grossly cystic craniopharyngiomas most of the problems related to the neoplastic mass may be, even if temporarily, improved by reducing volume of the cyst. A major surgical approach is unjustified when the aim is only to empty the cyst contents. Drainage of the cyst cavity by means of derivative techniques may be as effective and less invasive; in combined management plans that such tumours often require, they are, therefore, useful complementary procedures that can achieve long-lasting relief of symptoms, provided that the cyst is unilocular. Technical features and indications for such methods, with special regard to the techniques of sump drainage and of tube ventriculocystostomy, are discussed on the basis of the few reported series and of 6 personal cases. Usually only palliative aims are achieved, waiting for more definitive treatment; in a few selected cases, however, they may be quite effective.

Clinical review of nucleus caudalis dorsal root entry zone lesions for facial pain.

Twenty-seven patients with intractable facial pain underwent dorsal root entry zone thermocoagulation lesion of the nucleus caudalis of the spinal trigeminal nucleus. Retrospective review revealed a success rate of 85% in the immediate postoperative period declining to 52% on subsequent follow-up. The best results were in the subgroup of patients with postherpetic neuralgia, of which 67% achieved definite relief. There tended to be some correlation of satisfactory results and pain quality as well as extent of pain along trigeminal territory. The operative morbidity was low although most patients were observed to have a mild transient ipsilateral dysmetria.

Nucleus caudalis DREZ lesions for facial pain.

The records of the first 18 patients with intractable facial pain treated with nucleus caudalis dorsal root entry zone lesions were reviewed. The pain etiology varied but the largest group was that of post-herpetic neuralgia. Within the immediate postoperative period 90% of patients had satisfactory pain relief in comparison to 58% on subsequent follow-up. Seventy-one percent of those with post-herpetic neuralgia had satisfactory relief on subsequent follow-up. Favorable results tended to correlate with a lesser preoperative sensory deficit, pain restricted to trigeminal distributions and pain of a burning or lancinating/penetrating quality.

[Experiences in experimental microneurosurgery]. / Expériences en micro-neuro-chirurgie expérimentale.

The authors present their experiences in experimental micro-neuro-surgery referring to the last 2 years. In the field of vascular microsurgery, they explored: the possibility of performing end-to-side anastomoses reducing to few minutes the blood flow interruption in the receiving vessel; experimental reconstructive techniques of the arterial wall in case of giant aneurysm; micro-anastomoses between vessels with calibre smaller than 1 mm. The possibility of carrying out nervous anastomoses between intercostal and lumbar nerves to re-innervate these latter has been also examined on the basis of experimental trials.

Experimental model of nervous anastomosis between intercostal and lumbar nerves in the rabbit.

The authors propose a new experimental model of nervous anastomosis between intercostal and lumbar nerves in rabbit with the purpose of providing a technique to by-pass a spinal lesion. Before carrying out the surgical experiments, an histological study has been performed on the donor and receiver nerves which demonstrated the great difference in number of nervous fiber between these two nerves. The purpose of the method is thus to reinnerve a lumbar nerve by means of two intercostal nerves. Histological controls are performed on the 120th day.