Cortical plasticity after hand prostheses use: Is the hypothesis of deafferented cortex "invasion" always true?

OBJECTIVE: To study motor cortex plasticity after a period of training with a new prototype of bidirectional hand prosthesis in three left trans-radial amputees, correlating these changes with the modification of Phantom Limb Pain (PLP) in the same period. METHODS: Each subject underwent a brain motor mapping with Transcranial Magnetic Stimulation (TMS) and PLP evaluation with questionnaires during a six-month training with a prototype of bidirectional hand prosthesis. RESULTS: The baseline motor maps showed in all three amputees a smaller area of muscles representation of the amputated side compared to the intact limb. After training, there was a partial reversal of the baseline asymmetry. The two subjects affected by PLP experienced a statistically significant reduction of pain. CONCLUSIONS: Two apparently opposite findings, the invasion of the "deafferented" cortex by neighbouring areas and the "persistence" of neural structures after amputation, could vary according to different target used for measurement. Our results do not support a correlation between PLP and motor cortical changes. SIGNIFICANCE: The selection of the target and of the task is essential for studies investigating motor brain plasticity. This study boosts against a direct and unique role of motor cortical changes on PLP genesis.

Synchronous bilateral adrenalectomy in ACTH-dependent hypercortisolism: predictors, biomarkers and outcomes.

INTRODUCTION: Hypercortisolism requires a prompt therapeutic management to reduce the risk of development of a potential fatal emergency. A synchronous bilateral adrenalectomy (SBA) is effective in recovering hypercortisolism. However, specific indications for an SBA are not available. We aimed to evaluate the outcome of patients who underwent an SBA and to identify biomarkers able to predict the requirements of an SBA. PATIENTS AND METHODS: A mono-centric and longitudinal study was conducted on 19 consecutive patients who underwent SBA for ACTH-dependent hypercortisolism between December 2003 and December 2017. This study population was compared to two control groups composed of patients cured after the resection of the ACTH secreting pituitary adenoma (Group A: 44 patients) and of the ACTH-secreting neuroendocrine tumours (Group B: 8 patients). RESULTS: Short- or long-term SBA complications or the recurrence of hypercortisolism did not occur. A single patient experienced Nelson syndrome. Clinical features after SBA showed improvement in the glico-metabolic assessment, hypertension, bone metabolism and the occurrence of hypokalaemia and infections. The younger the age at the time of Cushing's disease diagnosis, the longer the duration of active hypercortisolism, higher values of plasmatic ACTH and Cortisol (1 month after pituitary neurosurgery) and higher values of Ki67 in pituitary adenomas were detected in this study population as compared to Group A. CONCLUSIONS: SBA is an effective and safe treatment for patients with unmanageable ACTH-dependent hypercortisolism. A multidisciplinary team in a referral centre with a high volume of patients is strongly recommended for the management of these patients and the identification of patients, for better surgical timing.

Primary hemorrhagic intramedullary melanoma. Case report with emphasis on the difficult preoperative diagnosis.

Primary melanoma of the central nervous system (CNS) is rare and primary spinal melanoma (PSM) is even more unusual. Preoperative diagnosis of melanocytic lesion as a PSM is difficult, because of the heterogeneous magnetic resonance (MR) signal intensity, due to hemorrhagic foci and melanin deposits. We describe the case of a 68 year-old male with a MR showing at Th8-Th9 level a well-defined intramedullary lesion; for the characteristics of hemorrhagic signal on MR and its association with a presumptive brain cavernoma, a preoperative diagnosis of intramedullary cavernous angioma was suspected. Pathological examination revealed a melanoma, and for the absence of other localizations outside the spinal cord, a diagnosis of primary spinal melanoma was established. The growth of PSM is slower and survival is longer than in the most common spinal metastasis from skin melanoma. Patients who undergo surgical excision, alone or associated with additional treatments, often show a long survival. We report this case to underline the importance and difficulties concerning the preoperative diagnosis of a hemorrhagic intramedullary lesion.

End-to-side nerve neurorrhaphy: critical appraisal of experimental and clinical data.

End-to-side neurorrhaphy (ESN) or terminolateral neurorraphy consists of connecting the distal stump of a transected nerve, named the recipient nerve, to the side of an intact adjacent nerve, named the donor nerve, "in which only an epineurial window is performed". This procedure was reintroduced in 1994 by Viterbo, who presented a report on an experimental study in rats. Several experimental and clinical studies followed this report with various and sometimes conflicting results. In this paper we present a review of the pertinent literature. Our personal experience using a sort of end-to-side nerve anastomosis, in which the donor nerve is partially transected, is also presented and compared with ESN as defined above. When the proximal nerve stump of a transected nerve is not available, ESN, which is claimed to permit anatomic and functional preservation of the donor nerve, seems an attractive technique, though yet not proven to be effective. Deliberate axotomy of the donor nerve yields results that are proportional to the entity of axotomy, but such technique, though resembling ESN, is an end-to-end neurorrhaphy. Neither experimental or clinical evidence support liberalizing the clinical use of ESN, a procedure with only an epineurial window in the donor nerve and without deliberate axotomy. Much more experimental investigation needs to be done to explain the ability of normal, intact nerves to sprout laterally. Such procedure appears justified only in an investigational setting.

Preliminary experience with 4K ultra-high definition endoscope: analysis of pros and cons in skull base surgery.

During the last two decades endoscopic skull base surgery observed a continuous technical and technological development 3D endoscopy and ultra High Definition (HD) endoscopy have provided great advances in terms of visualisation and spatial resolution. Ultra-high definition (UHD) 4K systems, recently introduced in the clinical practice, will shape next steps forward especially in skull base surgery field. Patients were operated on through transnasal transsphenoidal endoscopic approaches performed using Olympus NBI 4K UHD endoscope with a 4 mm 0° Ultra Telescope, 300 W xenon lamp (CLV-S400) predisposed for narrow band imaging (NBI) technology connected through a camera head to a high-quality control unit (OTV-S400 - VISERA 4K UHD) (Olympus Corporation, Tokyo, Japan). Two screens are used, one 31" Monitor - (LMD-X310S) and one main ultra-HD 55" screen optimised for UHD image reproduction (LMD-X550S). In selected cases, we used a navigation system (Stealthstation S7, Medtronic, Minneapolis, MN, US). We evaluated 22 pituitary adenomas (86.3% macroadenomas; 13.7% microadenomas). 50% were not functional (NF), 22.8% GH, 18.2% ACTH, 9% PRL-secreting. Three of 22 were recurrences. In 91% of cases we achieved total removal, while in 9% near total resection. A mean follow-up of 187 days and average length of hospitalisation was 3.09 ± 0.61 days. Surgical duration was 128.18± 30.74 minutes. We experienced only 1 case of intraoperative low flow fistula with no further complications. None of the cases required any post- or intraoperative blood transfusion. The visualisation and high resolution of the operative field provided a very detailed view of all anatomical structures and pathologies allowing an improvement in safety and efficacy of the surgical procedure. The operative time was similar to the standard 2D HD and 3D procedures and the physical strain was also comparable to others in terms of ergonomics and weight.

Molecular basis of extended-spectrum beta-lactamase production in nosocomial isolates of Klebsiella pneumoniae from Mérida, Venezuela.

Twelve Klebsiella pneumoniae isolates resistant to expanded-spectrum cephalosporins and aztreonam, from patients with nosocomial septicaemia at the intensive care unit of the Andes University Hospital, Mérida, Venezuela, were studied for production of extended-spectrum beta-lactamase (ESbetaL) activity. All were also resistant to gentamicin, kanamycin, tetracycline and chloramphenicol but sensitive to cefoxitin, imipenem, amikacin and tobramycin. Production of ESbetaL activity was confirmed by restoring susceptibility to ceftazidime in the presence of clavulanic acid. All isolates carried an identical plasmid of approximately 87 kb. Resistance to beta-lactams, aminoglycosides, tetracycline and chloramphenicol was lost en bloc after plasmid curing by treatment with acridine orange and was transferable en bloc to Escherichia coli by conjugation. Transconjugants always showed the same plasmid profile as that of Klebsiella donors. Isoelectric focusing analysis of the crude extracts of transconjugants showed in all cases, the presence of two beta-lactamases of pI 5.4 and 8.2. Analysis of the plasmid carried by one of the transconjugants by means of hybridization assays, revealed the presence of both bla(TEM) and bla(SHV) determinants. Cloning and sequencing of each determinant identified them as bla(TEM-1) and bla(SHV-5), respectively, the latter being responsible for the ESbetaL activity. Results of this study indicate that ESbetaL determinants of the SHV-type carried by transferable elements, are spreading among nosocomial isolates of K. pneumoniae in Mérida, Venezuela.

Quantitative, morphological, and somatotopic nuclear changes after facial nerve regeneration in adult rats: a possible challenge to the "no new neurons" dogma.

The anatomic reorganization of the subnucleus that controls the stylohyoid muscle (the stylohyoid subnucleus) within the brain stem facial nucleus was studied after regeneration of the facial nerve in adult rats. Horseradish peroxidase was injected into the right stylohyoid muscle 3 to 21 months after transection and repair of the right facial nerve at the level of the stylomastoid foramen. Position, number, and soma diameter of retrogradely horseradish peroxidase-labeled motoneurons were established, as well as the rostro-caudal extension of the stylohyoid subnucleus. In experimental rats, the stylohyoid subnucleus showed either an ipsilateral (50% of the rats) or a bilateral representation. In all of the experimental rats, the motoneurons composing the stylohyoid subnucleus had a more dispersed horizontal distribution pattern when compared with controls. More than 80% of the motoneurons were located outside the borders of the normal stylohyoid subnucleus, either ventrally or, especially in the rostral sections, dorsally closer to the floor of the fourth ventricle. The mean rostro-caudal length of the stylohyoid subnucleus was 2028.6 +/- 152.7 microns. The mean motoneuron number was 481.4 +/- 109.5 (2.20-fold greater than control values), and the motoneuron diameter distribution ranged from 7 to 43 microns. This study demonstrates that after regeneration of the facial nerve in adult rats, major changes occur in both the location and number of motoneurons that make up the stylohyoid subnucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Reconstruction of peripheral nerves: the phenomenon of bilateral reinnervation of muscles originally innervated by unilateral motoneurons.

It is well known that after reconstruction of sectioned peripheral nerves in adult mammals, denervated muscles are reinnervated by the axotomized motoneurons lying in the original motonucleus. It is less well known that these muscles can also be reinnervated by uninjured motoneurons lying in the homologous contralateral motonucleus. Therefore, after nerve reconstruction, bilateral motoneuron reinnervation of muscles can occur. Contralateral motoneurons sprout axons that cross the midline, grow in the reconstructed nerve, and reach muscle targets. This phenomenon was observed after reconstruction of several different peripheral nerves in adult mammals, including the oculomotor nerve in guinea pigs and the facial and sciatic nerves in rats. The retrograde axonal transport of horseradish peroxidase was used for the study of the organization of the brainstem and spinal cord motonuclei. Horseradish peroxidase was injected into the medial rectus muscle, the stylohyoid muscle, and the trunk of the sciatic nerve. The distance between the homologous motonuclei of both sides influenced the occurrence of this phenomenon. In fact, bilateral reinnervation of muscles after nerve reconstruction was found in 36% (sciatic nerve), 50% (facial nerve), and 100% (oculomotor nerve) of the operated animals. The total number of contralateral motoneurons found were 14% (oculomotor nerve), 8% (facial nerve), and 5% (sciatic nerve). Bilateral reinnervation of muscles was evoked by both immediate and delayed peripheral nerve repair and was a stable phenomenon, seen between 3 and 21 months after facial nerve reconstruction.

Spinal cord transection in adult rats: effects of local infusion of nerve growth factor on the corticospinal tract axons.

The spinal cord of adult female rats was completely transected at the T8 level. Nerve growth factor (NGF) was administered at the lesion site via indwelling, implanted, osmotic minipumps. Purified NGF was supplied at doses of 100, 200, and 500 micrograms during a 30-day period. Control rats were treated with saline. At the end of the treatment, the proximal stump of corticospinal tract axons in the spinal cord was labeled with anterograde transported horseradish peroxidase (HRP) injected into the sensorimotor cortex. In control rats, the corticospinal tract axons ended abruptly, proximal to the zone of maximal damage. Sterile swellings developed at the axon tips, and no labeled axonal sprouts were apparent. On the contrary, in NGF-treated animals, the leading front of the corticospinal tract axons showed a trend of approaching the zone of maximal damage following abnormal paths through the dorsal-injured white matter. Axonal sprouts were seen more proximally, traveling toward the transection site in aberrantly located dorsal paths, completely outside the normal position of the corticospinal tract. NGF seems to partly restore the pattern of the regenerative behavior of the severed corticospinal tract axons after spinal cord transection in newborn rats, i.e., the induction of axonal sprouting in aberrantly located dorsal paths. An automated image analysis of the HRP reaction field close to the transection site demonstrated that the density of HRP-labeled axons in the corticospinal tract was significantly higher in the NGF-treated rats than in the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Radial nerve palsy caused by spontaneously occurring nerve torsion. Case report.

An 18-year-old man presented with a spontaneously occurring radial nerve palsy that spared the triceps muscle. At surgery, the portion of the radial nerve located at the midarm level had an hourglass-like appearance. Under magnification, an external-internal neurolysis of the narrowed portion of the hourglass-shaped portion revealed nerve torsion. Straightening of the twisted nerve and fixation accomplished using epiperineurium-fascia stitches to avoid a new torsion resulted in complete functional recovery of the radial nerve.

Experimental repair of the oculomotor nerve: the anatomical paradigms of functional regeneration.

In adult guinea pigs, the oculomotor nerve was sectioned proximally (at the tentorial edge) or more distally (at the orbital fissure) and immediately repaired by reapproximation. During a 24-week postoperative period, extrinsic eye motility was assessed by analyzing the vestibulo-ocular reflexes. The regenerated oculomotor nerve was studied morphometrically on semi-thin histological sections at 16 and 24 weeks postinjury. The selectivity of muscle reinnervation was investigated by injection of both single (horseradish peroxidase) and double (fluorescent dyes) retrograde axonal tracers into the eye muscles. Following proximal repair of the oculomotor nerve, the degree of recovery of extraocular motility varied among different animals and remained stable over long-term observations. In animals with poor recovery, aberrant eye movements were always found, and the somatotopic map of the reinnervated eye muscles was greatly altered. Distortions of the central representation were also seen in those animals in which a good level of functional recovery was seen. However, in animals with good recovery, a topographic bias was re-established by about 65% of the original neuronal population, as opposed to 26% in the animals with poor recovery. Neurons located contralateral to the axotomized nucleus sprouted intra-axially and projected their axons to denervated eye muscles. The number and diameter of the regenerated axons, the number and soma diameter of the axotomized neurons, and the ratio of distal axonal branches to proximal supporting neurons were all related to the degree of functional recovery. Following repair of the oculomotor nerve at the orbital fissure, extraocular motility had recovered in all of the animals at 16 weeks without aberrant phenomena. Functional regeneration of the distally transected oculomotor nerve is thought to be the result of selective muscle reinnervation.

Neurofibromatosis type 2: growth stimulation of mixed acoustic schwannoma by concurrent adjacent meningioma: possible role of growth factors. Case report.

The authors report the case of a young man suffering from neurofibromatosis type 2 (NF2) who harbored bilateral acoustic schwannomas and a parasellar meningioma. Neuroimaging studies performed during a 4-year follow-up period showed that the bilateral schwannomas had grown very little and at similar rates. However, after the meningioma had infiltrated the tentorium and approached the ipsilateral schwannoma at the incisura, both Schwann cell tumors started to grow rapidly, particularly the one adjacent to the meningioma, of which the percentage of annual growth rate increased by approximately a factor of 10(2). At the same time, magnetic resonance imaging showed that this tumor also changed its features. During surgery, the acoustic schwannoma was firmly adherent to both meningioma and tentorium. Histological examination revealed meningotheliomatous cells in the schwannoma adjacent to the meningioma. Antiphosphotyrosine immunoblotting of PC12 cells was compatible with the presence of an epidermal growth factor (EGF)-like molecule in the cerebrospinal fluid (CSF) of the patient. This factor was not detected in the CSF of five other NF2 patients, two of whom bore associated bilateral acoustic schwannomas and meningioma in remote locations. It is hypothesized that the meningotheliomatous cells infiltrating the schwannoma triggered an autocrine/paracrine growth-stimulatory mechanism that involved an EGF-like factor.

Superior cervical ganglion regenerating axons through peripheral nerve grafts and reversal of behavioral deficits in hemiparkinsonian rats.

The superior cervical ganglion (SCG) has been grafted to the brain of adult rats in an attempt to reverse the parkinsonian syndrome that follows destruction of central dopamine systems. However, the main limitation to this approach is the massive cell death that occurs in the grafted SCG after direct transplantation into the brain. In adult rats, 6-hydroxydopamine (6-OHDA) was stereotactically injected into the right substantia nigra (SN). One month later, dopamine denervation was assessed using the apomorphine-induced rotational test. In rats with a positive test, an autologous peripheral nerve (PN) graft was tunneled from the right cervical region to the ipsilateral parietal cortex. One end of PN graft was sutured to the transected postganglionic branch of the SCG and the other end was inserted into a surgically created cortical cavity. The apomorphine test was repeated at 3 days and again at 1, 3, and 5 months after surgery. The brain, SCG, and PN graft were studied under light and electron microscopy and with the tyrosine hydroxylase immunohistochemical and horseradish peroxidase tracing methods. Three days after grafting, there were no significant differences on the apomorphine test as compared to the preoperative test. Conversely, 1,3, and 5 months after grafting, the number of rotations was reduced by 69% (+/-20.2), 66.6% (+/-17.1), and 72.5% (+/-11.3), respectively. Control rats that received a free PN graft to the brain and underwent section of the postganglionic branch of the SCG did not show significant changes on the apomorphine test after surgery. Histological examination revealed that the PN graft was mostly reinnervated by amyelinic axons of small caliber. Approximately 40% of the SCG neuronal population that normally projects to the postganglionic branch survived axotomy and regenerated the transected axons into the PN graft. Axons arising from the SCG elongated the whole length of the graft, crossed the graft-brain interface and extended into brain regions adjacent to the denervated striatum up to 2037 micrometer from the graft insertion site. This work shows that the ingrowth of catecholamine-regenerating axons from the SCG to dopamine-depleted brain parenchyma significantly reduces behavioral abnormalities in hemiparkinsonian rats. This effect cannot be ascribed either to the brain cavitation or to the PN tissue placement in the brain.

Effect of magnesium valproate on amygdala-kindled seizures in the rat: comparison with sodium valproate.

The anticonvulsant activity of a salt of valproic acid (VA), magnesium valproate (MgV), was assessed against amygdala-kindled seizures in rats. The anti-epileptic power of MgV was compared with that of sodium valproate (NaV). Kindling was obtained by delivering daily to one of the amygdala a 2 s train of monophasic square-wave pulses (1 ms, 60 c.p.s., 100-130 microA) via chronically implanted electrodes. Magnesium valproate and NaV were tested once kindling was stabilized and the post-kindling threshold for generalized convulsions was determined. The drugs were administered intraperitoneally in doses ranging from 25 to 200 mg/kg. The injection/test interval was 30 min. Each animal received a single dose every 24 h. Magnesium valproate exhibited an anticonvulsant activity qualitatively and quantitatively similar to that of NaV. Statistically significant differences were not found between the two drugs with respect to the reduction of seizure severity and afterdischarge (AD) duration. The calculated ED50's were 94.58 and 97.41 mg/kg for the suppression of generalized seizures, 176.96 and 129.26 mg/kg for the suppression of partial seizures, 275.96 and 224.13 mg/kg for the suppression of the local AD in the MgV and NaV treated groups, respectively.

Effects of levo-acetylcarnitine on second motoneuron survival after axotomy.

Little is known about factors that regulate the survival of cranial motoneurons which project to peripheral targets. Various neurotrophic factors of central and peripheral origin have been isolated. In this study, we examined thirteen newborn Wistar rats to determine the effects of acetyl-L-carnitine treatment on the survival of motoneurons within the facial nucleus after transection of the facial nerve. Acetyl-L-carnitine was administered for 7 days in seven rats after nerve transection, while saline solution was injected in 6 rats used as controls. Both the motoneuron number and the motoneuron diameter were significantly higher in the facial nucleus of the rats treated with acetyl-L-carnitine than in the facial nucleus of the control rats. The results obtained suggest that acetyl-L-carnitine can rescue a substantial number of facial motoneurons from axotomy-induced cell death. Compared to neurotrophic factors, because of its simple molecular structure, acetyl-L-carnitine permits a safe oral and parenteral administration. It is suggested that acetyl-L-carnitine could be considered for use as a therapeutic agent in neurodegenerative disorders.

Callosotomy for generalized seizures associated with hypothalamic hamartoma.

A case is reported of intractable epilepsy associated with a hypothalamic hamartoma in an 18 year old man. The patient underwent a two-third anterior callsotomy and, subsequently, removal of the hamartoma. Callosotomy did not affect the generalized seizure pattern. The authors believe this to be the first documented case of hypothalamic hamartoma in which callosotomy for seizure control was attempted. The poor response to callosotomy suggests the extracallosal diffusion of the generalized seizures from hypothalamic hamartomas.

Acrylic hydrogel implants after spinal cord lesion in the adult rat.

Acrylic hydrogels, like the polymer of 2-hydroxyethyl methacrylate, are biocompatible, mechanically stable, porous materials that can be coated with collagen or laminin acting as bioadhesive substrates. Poly-2-hydroxyethyl methacrylate sponges have been proposed for restoring the anatomical continuity of damaged neural structures. In the present work, the ability of poly-2-hydroxyethyl methacrylate sponges to provide the injured spinal cord neurons with a conductive substrate for their regenerating axons was investigated in 32 adult Wistar rats. Collagen impregnated poly-2-hydroxyethyl methacrylate sponges were implanted into suction cavities of the dorsal funiculus of the spinal cord. Two to four months after implantation, the spinal cord was removed and processed for histology, and S100 and GFAP immunohistochemistry. To study axonal regeneration into the sponge, the spinal cord or the sensorimotor cortex were injected with 0.05-0.1 microl of an 8% solution of lectin-conjugated horseradish peroxidase or 10% dextran tetramethylrhodamine. The fibroglial reaction, accumulation of mononuclear cells, and angiogenesis at the interface between the spinal cord and the sponge were minimal. Cystic cavitation in the spinal cord was virtually absent. Anterograde labeled axons were seen to penetrate and to elongate the full length of the sponge. These results demonstrate that poly-2-hydroxyethyl methacrylate sponges represent a safe supportive material for regenerating spinal cord axons.