Peripheral nerve field stimulation for chronic neuropathic pain: a single institution experience.

BACKGROUND: Peripheral nerve field stimulation (PNFS) is a novel neurosurgical procedure consisting of implantation of subcutaneous leads in specific painful areas in different types of painful, drug-resistant syndromes. The objective of this study was to evaluate the efficacy of PNFS in several patients affected by different chronic neuropathic pain syndromes, along with its risks, limits and possible correlation between the results achieved and the patients' main symptoms. METHODS: Twenty-two patients affected by different types of chronic neuropathic pain were submitted to PNFS at the Department of Neurosurgery of the Istituto Neurologico "C. Besta" in Milan between July 2009 and July 2013. The visual analog scale (VAS) and variations in the use of analgesic drugs, along with complications, were considered to assess results. RESULTS: In 59 % of our patients, an average pain reduction of 5.50 points on the visual analog scale was observed (average pre-implant score 8.86 and average post-implant score 3.36). These patients reduced their analgesic drug use after PNFS. We observed no early or long-term complications after our last follow-up evaluation. CONCLUSIONS: PNFS can be considered an effective and safe option to treat carefully selected, drug-resistant and chronic neuropathic pain patients; the reversibility of the procedure and its lack, at least in our hands, of long-term complications may contribute to wider use of this procedure.

A modified visual analogue scale for the assessment of chronic pain.

The present common evaluation of pain is scored through the use of visual analogue scale (VAS) to assess the intensity of pain and, sometimes, an additional table in which the frequency of pain attacks during the day is reported. We propose a modified 2D-VAS to assess both the intensity and the frequency (expressed by the percentage of the time in which pain is experienced during the day). Thus with only one scale and graphic representation, we can have a clear picture of the patient's condition before and during any treatment to relieve his pain.

A case of very long-term appearing drug tolerance to intrathecal baclofen.

A 66-year-old man affected by familial spastic paraplegia since he was 22 developed drug tolerance to intrathecal baclofen after 16 years of treatment A stable dosage of 850 microg/day, achieved after the first two years, appeared to be progressively inadeguate to relief his spasticity. No other evidence of additional diseases or progression of his neurological disease were recognized. The daily dosage was then increased to 1200 microg/day without any decrease in spasticity or improvement in the patient's motor performance. Thus a slow and progressive decrease of the daily dosage was performer by 10% each 15 days while the patient's clinical condition was monitored. The patient reached a complete withdrawal of the baclofen administration experiencing the same spasticity and motor performance he experienced at the beginning of his therapy with intrathecal baclofen in 1991. The patient was then kept on drug holiday for three months without any variation in his clinical picture. A stabilized daily baclofen dosage of 250 microg was then reached to maintain the same improvement of motor performance that the patient had experienced before the onset of drug-tolerance signs. Some cases of drug tolerance to intrathecal baclofen were previously reported but this is an original case of very long-term onset of this phenomenon.

Intrathecal baclofen for the treatment of spasticity.

Spasticity is a clinical condition characterized by a velocity-dependent increase of muscle tone due to "parapyramidal" disturbance of the inhibitory afferents to the second motor neuron. Intrathecal baclofen (ITB) is at present the most effective treatment tor generalized spasticity provided that an accurate assessment of patients to be candidates for ITB is made. The most important patient ,election criterion is lack of positive response to any oral antispastic drug or appearance of undesired side effects of such oral treatment. Spasticity should not be treated in patients in whom it may be helpful to maintain posture due to their very poor muscle strength. When assessing a spastic patient alternative treatments such as Botox and peripheral neurotomies must also be considered, particularly in cases of predominantly focal spasticity. According to our experience, it is advisable to divide spastic patients into two different groups: the first group including wheel-chaired and bed-ridden patients, the second group comprising spastic patients who are still able to move. In each of these two groups treatment goals vary and require different protocols for the patients' evaluation. Assessment of patients is completed with the functional index measurement (FIM) scale in order evaluate changes in patients' quality of life caused by variations in the motor performance. Currently, treatment of spasticity with ITB is the most effective way of reducing spasticity regardless of its cause.

The guidelines for the diagnosis and treatment of spasticity.

Spasticity is a predominant clinical sign appearing in different neurological diseases. It is always flanked by various degrees of muscle weakness. The clinical evaluation of a spastic patient is score according to varius internationally approved evaluation scales (Ashworth scale, muscle spasms scale, and FIM disability scale). The treatment of spasticity is mostly a symptomatic treatment aimed to relief muscle hypertonus thus increasing both motor performance and improving nursing. Many molecules are frequently being used orally with poor results or with the onset of undesired side effects. In fact oral baclofen, diazepam and tizanidine often have poor effect on spasticity and bring frequently to the appearance of undesired side effects caused by the concentration of these molecule at the brain level. Intrathecal baclofen is a good option to treat diffuse spasticity through the infusion of baclofen into the spinal CSF space. When baclofen is administered intrathecally at the spinal level it distributes with a concentration-gradient between caudal and rostral level of the spine that was calculated as 4:1 thus avoiding its concentration at the brain level when given at a therapeutical dosage. This fact avoids any undesired side effect due to the action of baclofen at the brain level. Botulinum toxin as well as peripheral neurotomies are very helpful in those cases in whom spasticity is mainly restricted to few muscular groups. A correct flow-chart to diagnose and treat the patient is mandatory to achieve the best results for each patient according to his spasticity and residual motor ability.

Linkage disequilibrium analysis of Friedreich's ataxia in 140 Caucasian families: positioning of the disease locus and evaluation of allelic heterogeneity.

We investigated linkage disequilibrium between Friedreich's ataxia (FRDA) and four tightly linked multi-allele markers in 140 families from France and Italy. These markers include three microsatellites (D9S111, D9S15 and D9S110) and one RFLP (D9S5). Their chromosomal order, D9S111-D9S15-D9S110-D9S5, had previously been established by physical mapping. Linkage disequilibrium was evaluated between each marker and FRDA and between markers. Extended haplotypes were obtained and their frequencies on FRDA and normal chromosomes were evaluated. We obtained evidence of strong allelic association of FRDA with D9S5 only. Analysis of linkage disequilibrium between markers revealed a significant decrease between D9S110 and D9S5, suggesting the presence of a recombination hot spot in the interval between these markers. Probably for this reason, no major FRDA-associated extended haplotype could be identified. Our data suggest the presence of a few common disease-causing mutations in the examined population, and indicate a putative localization for the FRDA gene. Transcribed sequences have been found in this candidate region.

Calcium and magnesium content in fetuses at risk and prenecrotic Duchenne muscular dystrophy.

We measured calcium (Ca) and magnesium (Mg) content in muscles of fetuses at risk of Duchenne muscular dystrophy (DMD) and in a premature infant who later developed typical DMD. There was a three- to six-fold increase in muscle Ca in the fetuses and in the premature infant. In contrast to our previous reports of reduced muscle Mg in DMD children, there was an 18 to 57% increase of Mg in the fetuses at risk. Opaque and Ca-positive fibers, rarely observed in normal fetuses, were numerous in fetuses at risk and in the premature infant. No necrotic fibers were detected in the fetuses or the premature infant. These findings suggest that excessive Ca accumulation precedes necrosis in DMD. Other factors related to growth and development that occur after birth may trigger the necrosis that follows muscle Ca accumulation.

Transillumination in minimally invasive surgery for carpal tunnel release. Technical note.

An alternative technique for performing minimally invasive release of carpal tunnel syndrome is described. The suggested methodology is based on transillumination of the carpal tunnel during surgery. The advantages of the technique are discussed and compared with other available surgical procedures including endoscopy. The authors also describe preliminary operative results in 50 consecutive patients.

The treatment of spasticity by intrathecal administration of baclofen: a preliminary personal experience.

The administration of baclofen, a GABAb agonist, by direct infusion into the CSF by means of a programmable device, may avoid the undesired side effects of the oral administration of both the same and other antispastic drugs while giving a marked reduction of spasticity. The preliminary results on 12 patients show the total efficacy of this procedure in reducing spasticity markedly.

Neurophysiological monitoring of cranial nerves during posterior fossa surgery.

Intraoperative neurophysiological monitoring of cranial nerve functions in surgery for microvascular decompression and tumors of the posterior fossa is important for minimizing risk of permanent damage to the nerves. In particular, intraoperative BAEP and the EMG function of muscle innervated by trigeminal and facial muscle have been found useful. We report here our experiences with intraoperative monitoring of brainstem auditory evoked potentials (BAEP) and EMG recorded from muscles supplied by the trigeminal and facial nerves.

A neurophysiological method for the evaluation of motor performance in spastic walking patients.

Intrathecal baclofen is at present the best treatment for severe spasticity of various etiologies. In walking patients affected by severe spasticity a careful evaluation of the motor performance is needed for a correct indication for this treatment. The examination should focus on the delicate balance between spasticity and voluntary muscle activation which is crucial for an improvement of motor performance during gait. Seven patients have been neurophysiologically evaluated by the use of a Cibex apparatus measuring torque and movement velocity of the lower limbs simultaneously with static and dynamic recordings of the EMG.

[Contribution of thalamotomy, cordotomy and dorsal root entry zone Caudalis trigeminalis lesions in the treatment of chronic pain]. / Le rôle de la thalamotomie, de la cordotomie et de la lésion de la dorsal root entry zone (DREZ) Caudalis trigeminalis dans le traitement de la douleur chronique.

Ablative neurosurgical methods are mainly proposed in cases of nociceptive pain, but, at present, medical treatments and local pharmacotherapy (intrathecal and intracerebroventricular) are often very effective in this context. Moreover, neuropathic pain is well controlled by äugmentative techniques, except painful paroxysms. If a destructrive method is necessary, it is selective, performed according to precise neurophysiological and anatomical data with the frequent use of percutaneous and/or stereotactic techniques: the lesion of caudalis DREZ in treatment of neuropathic trigeminal pain, the antero-lateral cordotomy in the treatment of unilateral severe cancer pain and several kinds of thalamotomy.

Muscle fiber degeneration and necrosis in muscular dystrophy and other muscle diseases: cytochemical and immunocytochemical data.

Serial consecutive frozen sections from 164 muscle biopsy specimens were studied cytochemically. We localized calcium and albumin as endogenous markers of extracellular fluid penetration and C3 and C9 complement components as markers of muscle fiber necrosis. In both Duchenne dystrophy and congenital muscular dystrophy, a significant percentage of fibers were overloaded with calcium and penetrated by albumin. Most of these fibers appeared opaque with trichrome stain. C3 and C9 complement components appeared only in necrotic fibers, which invariably were also penetrated by albumin. These observations support previous findings that muscle fiber necrosis is linked to massive inflow of extracellular fluid and complement activation. In addition, in both Duchenne and congenital dystrophies, numerous nonnecrotic fibers are penetrated by calcium-rich extracellular fluid.

Italian multicentric study on pain treatment with epidural spinal cord stimulation.

A multicentric study on the treatment of nonmalignant chronic pain with epidural spinal cord stimulation (SCS) has been carried out in 32 Italian centers devoted to pain therapy. Neurosurgical and anesthesiology units participated in this retrospective study. 410 of the eligible patients were enrolled in the protocol: 48% were male, 52% female. All patients underwent a screening test period (average 21 days) and 74% underwent the definitive implant. The diagnosis was failed back surgery syndrome in 45%, reflex sympathetic dystrophy in 15%, phantom limb pain in 14%, postherpetic neuralgia in 8%, peripheral nerve injury in 5%, others 13%. 84% received noninvasive unsuccessful treatment (10 tensor acupuncture). All had previous pharmacological therapy which was not always discontinued when SCS took place. Pain assessment had been done with the visual analog scale and verbal scale both subjectively and by the physician and nurses. Neuropsychological profile with minimal mental test or MMPI was obtained in 68% of the patients. These results were favorable (i.e. excellent or good; more than 50% reduction of pain) in 87% of the patients at the 3-month follow-up, 75% at the 6-month follow-up, 69% at the 1-year follow-up, and 58% at the 2-year follow-up. Complication rate was: dislocation of the electrocatheter 4%, technical problems 3%, infections of the system 2%. The results will be discussed in correlation with the different etiologies of the nonmalignant chronic pain syndrome.

Life-threatening dystonia-dyskinesias in a child: successful treatment with bilateral pallidal stimulation.

We report a 13-year-old boy who developed severe, refractory dystonia-dyskinesias as an abrupt worsening of a previously nonprogressive movement disorder. The movements became continuous, requiring artificial respiration and continuous sedation in the intensive-care unit. Various drugs and drug combinations failed to achieve control. The child was then treated successfully with bilateral pallidal (GPi) stimulation as shown in the videotape. Four months later and without medication, the boy regained autonomous gait and audible speech; his neurologic condition continues to improve.

Fetal myosin immunoreactivity in human dystrophic muscle.

We report immunofluorescence observations on normal and dystrophic human muscle using an antibody (anti-bF) raised against bovine fetal myosin and specific for fetal myosin heavy chains. In rat skeletal muscle, anti-bF was previously found to react selectively with myosin isoforms expressed during fetal and early postnatal development and in regenerating muscles. Anti-bF stained most fibers in human fetal and neonatal muscle, whereas only nuclear chain fibers of muscle spindles were labeled in normal adult muscle. In muscle biopsies from patients with Duchenne's muscular dystrophy, numerous extrafusal fibers were stained: some were small regenerating fibers, others were larger fibers presumably resulting from previous regenerative events. Fetal myosin immunoreactivity in Duchenne's dystrophy appears to reflect the reexpression of fetal-specific myosin isoforms and provides a new valuable tool for identifying regenerating fibers and following their destiny in dystrophic muscle.

Microvascular decompression for trigeminal neuralgia: comments on a series of 250 cases, including 10 patients with multiple sclerosis.

OBJECTIVE: To examine surgical findings and results of microvascular decompression (MVD) for trigeminal neuralgia (TN), including patients with multiple sclerosis, to bring new insight about the role of microvascular compression in the pathogenesis of the disorder and the role of MVD in its treatment. METHODS: Between 1990 and 1998, 250 patients affected by trigeminal neuralgia underwent MVD in the Department of Neurosurgery of the "Istituto Nazionale Neurologico C Besta" in Milan. Limiting the review to the period 1991-6, to exclude the "learning period" (the first 50 cases) and patients with less than 1 year follow up, surgical findings and results were critically analysed in 148 consecutive cases, including 10 patients with multiple sclerosis. RESULTS: Vascular compression of the trigeminal nerve was found in all cases. The recurrence rate was 15.3% (follow up 1-7 years, mean 38 months). In five of 10 patients with multiple sclerosis an excellent result was achieved (follow up 12-39 months, mean 24 months). Patients with TN for more than 84 months did significantly worse than those with a shorter history (p<0.05). There was no mortality and most complications occurred in the learning period. Surgical complications were not related to age of the patients. CONCLUSIONS: Aetiopathogenesis of trigeminal neuralgia remains a mystery. These findings suggest a common neuromodulatory role of microvascular compression in both patients with or without multiple sclerosis rather than a direct causal role. MVD was found to be a safe and effective procedure to relieve typical TN in patients of all ages. It should be proposed as first choice surgery to all patients affected by TN, even in selected cases with multiple sclerosis, to give them the opportunity of pain relief without sensory deficits.

Image guided neuroendoscopy for third ventriculostomy.

Third ventriculostomy has become an increasing popular procedure for the treatment of hydrocephalus of different aetiologies. Between october 1997 and october 1998, 17 patients (12 females, 5 males; 12-82 year-old; mean age 43) underwent image-assisted endoscopic third ventriculostomy for hydrocephalus at the Istituto Nazionale Neurologico "C.Besta" of Milano. There was no mortality and no long term morbidity. Neuronavigation has been found useful in selecting the safest trajectory to the target avoiding any traction on the foramen of Monro related structures and allowing the necessary mobility for fine adjustments under visual and "tactile" control when choosing the safest point to perform the stoma. According to our experience neuro-endoscopy and neuronavigation seems to be complementary in reaching easy, safe and successful results in the treatment of hydrocephalus of different origins.

Needle biopsy for muscle diagnosis and research: an Italian experience.

We report our experience of needle biopsy over the past two and a half, viz. 395 cases. We find that the technique meets the needs of diagnosis and research very satisfactorily. We describe its advantages over open biopsy and recommend it in preference to the latter, provided that the necessary technical skill for processing the sample is available.

Friedreich ataxia in Italian families: genetic homogeneity and linkage disequilibrium with the marker loci D9S5 and D9S15.

Friedreich ataxia (FA) is an autosomal recessive degenerative disease of the nervous system of unknown biochemical cause. The FA gene has been shown to be in close linkage with the two chromosome 9 markers D9S5 and D9S15, and linkage disequilibrium between FA and D9S15 has been detected in French families by Hanauer et al. We used new highly informative markers at the above loci to analyze Italian FA families for linkage and linkage disequilibrium. The new markers were a three-allele BstXI RFLP at D9S5 (PIC = .55) and a six-allele microsatellite, typed by polymerase chain reaction, at D9S15 (PIC = .75). We obtained maximum lod scores of 8.25 between FA and D9S5, 10.55 between FA and D9S15, and 9.52 between D9S5 and D9S15, all at zero recombination. Our results, combined with those reported by other authors, reduce maxlod-1 (maximum lod score minus 1) confidence limits to less than 1.1 cM between FA and D9S5, 1.2 cM between FA and D9S15, and 1.4 cM between D9S5 and D9S15. Linkage disequilibrium with FA was found only for D9S15 when all families were evaluated but was also found for a D9S5/D9S15 haplotype in a subgroup of southern Italian families. We conclude that FA, D9S5, and D9S15 are tightly clustered and that studies of geographically restricted groups may reveal a limited number of mutations responsible for the disease in the Italian population. We present preliminary evidence from pulsed-field gel electrophoresis that D9S5 and D9S15 may be less than 450 kb apart. Linkage disequilibrium between FA and D9S15 suggests that the disease gene may be at an even shorter distance from this marker locus, which therefore represents a very good starting point for cloning attempts.