Treatment of progressive myopia with 0.01% Atropine in children and adolescents: an Italian 4-year follow-up study.

Purpose: To assess the effectiveness of atropine 0.01% in slowing the progression of myopia in young patients. Methods: 2,387 patients with progressive myopia (more than -0.50 spherical diopters increased in the last year) were enrolled. They received, every evening, one drop of atropine 0.01% in each eye. Refraction was then measured at baseline (T0) and once a year (T1, T2, T3, T4) for a 4-years follow-up period, and compared with a non-treated control group. Results: A reduction in the myopic progression was observed in the treated group respect to the control one. The average spherical refraction after 4 years increased by 27.06% in the treated group versus 241% of the control one. The difference in spherical increase between the two groups respect to time 0 was appreciable already at the first control, (T1 -T0, -0.21D vs. -1D) and continued to increase for all the 4-years follow-up period (T2-T0, -0.38D vs. -1.91D;T3-T0, -0.52D vs. -2.74D; T4-T0, -0.73D vs. -3.63D, respectively). It was always significant (P<0.01). Compared to the previous year, the average spherical increase was quite stable in the two groups (0.17 vs. 0.87, respectively). No significant tachyphylaxis or adverse effects were observed throughout the examination period. Conclusions: 0.01% atropine was effective in slowing the progression of myopia in the treated group vs. control one. The clinical effect was noticeable already from the first control, and continued for all the observation period. The results of this study agree with those already reported in literature, and confirm the validity of this treatment.

Results by motor cortex stimulation in treatment of focal dystonia, Parkinson's disease and post-ictal spasticity. The experience of the Italian Study Group of the Italian Neurosurgical Society.

Extradural motor cortex stimulation has been employed in cases of Parkinson's disease (PD), fixed dystonia (FD) and spastic hemiparesis (SH) following cerebral stroke. Symptoms of PD are improved by EMCS: results were evaluated on the basis of the UPDRS and statistically analysed. In PD EMCS is less efficacious than bilateral subthalamic nucleus (STN) stimulation, but it may be safely employed in patients not eligible for deep brain stimulation (DBS). The most rewarding effect is the improvement, in severely affected patients, of posture and gait. FD, unresponsive to bilateral pallidal stimulation, has been relieved by EDMS. In SH reduction of spasticiy by EMCS allows improvement of the motor function.

The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex.

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (TMS). When applied to motor cortex it leads to after-effects on corticospinal and corticocortical excitability that may reflect LTP/LTD-like synaptic effects. An inhibitory form of TBS (continuous, cTBS) suppresses MEPs, and spinal epidural recordings show this is due to suppression of the I1 volley evoked by TMS. Here we investigate whether the excitatory form of TBS (intermittent, iTBS) affects the same I-wave circuitry. We recorded corticospinal volleys evoked by single pulse TMS of the motor cortex before and after iTBS in three conscious patients who had an electrode implanted in the cervical epidural space for the control of pain. As in healthy subjects, iTBS increased MEPs, and this was accompanied by a significant increase in the amplitude of later I-waves, but not the I1 wave. In two of the patients we tested the excitability of the contralateral cortex and found a significant suppression of the late I-waves. The extent of the changes varied between the three patients, as did their age. To investigate whether age might be a significant contributor to the variability we examined the effect of iTBS on MEPs in 18 healthy subjects. iTBS facilitated MEPs evoked by TMS of the conditioned hemisphere and suppressed MEPs evoked by stimulation of the contralateral hemisphere. There was a slight but non-significant decline in MEP facilitation with age, suggesting that interindividual variability was more important than age in explaining our data. In a subgroup of 10 subjects we found that iTBS had no effect on the duration of the ipsilateral silent period suggesting that the reduction in contralateral MEPs was not due to an increase in ongoing transcallosal inhibition. In conclusion, iTBS affects the excitability of excitatory synaptic inputs to pyramidal tract neurones that are recruited by a TMS pulse, both in the stimulated hemisphere and in the contralateral hemisphere. However the circuits affected differ from those influenced by the inhibitory, cTBS, protocol. The implication is that cTBS and iTBS may have different therapeutic targets.

Neurophysiological aspects of chronic motor cortex stimulation.

Chronic motor cortex stimulation is a treatment option for neuropathic drug-resistant pain and possibly associated movement disorders. Preliminary studies suggest the possibility to treat symptoms of Parkinson disease in selected patients. Recently, MCS has been suggested to enhance motor recovery in patients with poststroke hemiparesis. One or more electrodes are placed extradurally over the motor cortex through a burr hole or a small craniotomy, and then connected to a totally implantable neurostimulator. The accurate positioning of the stimulating electrodes over the motor cortex is the key point of the surgical procedure. Motor cortex identification results from the integration of anatomical, neuroradiological, functional, and neurophysiological data, taking into account the huge population variability. Intraoperative neurophysiological mapping of the motor cortex is of paramount importance, in spite of very sophisticated neuroradiological mathematical reconstructions of the motor area. We discuss and compare the different techniques that are utilized by different authors. Moreover, clinical neurophysiology is also helpful in evaluating the results of this neuromodulation procedure and in hypothesizing the mechanisms that are put in play by MCS.

Motor cortex stimulation for chronic non-malignant pain: current state and future prospects.

Motor cortex stimulation (MCS) was proposed by Tsubokawa in 1991 for the treatment of post-stroke thalamic pain. Since that time, the indications have been increased and included trigeminal neuropathic pain and later other types of central and peripheral deafferentation pain. The results reported in the literature are quite good; the mean long-term success rate is 80% in facial pain and 53% in non-facial pain. Our own results are less impressive: 4 of 14 patients (28%) experienced a greater than 40% pain relief, but in 2 of them the effect faded with time. Only few minor complications have been reported. The accurate placement of the epidural electrode over the motor cortex that somatotopically corresponds to the painful area is believed to be essential for pain relief. Predictive factors included the response to pharmacological tests, the relative sparing from the disease process of the cortico-spinal tract and the sensory system, and the analgesic response achieved during the test period of MCS. A possible predictive factor might be a test of repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. MCS may act by rebalancing the control of non-nociceptive sensory inputs over nociceptive afferents at cortical, thalamic, brainstem and spinal level. In addition, it may interfere with the emotional component of nociceptive perception. Biochemical processes involving endorphins and GABA may also be implicated in the mechanism of MCS. It is time for a large multicenter prospective randomized double blind study evaluating not only the effect of MCS on pain (based on the available guidelines for assessment of neuropathic pain), but also the optimal electrode placement and stimulation parameters, and the possible relationship with the response to rTMS. New electrode design and a new generation of stimulators may help in improving the results.

Retrospective analysis of variables favouring good surgical outcome in posterior epilepsies.

AIM: to determine variables favouring good surgical outcome in posterior epilepsies. METHODS: Fourteen patients submitted to epilepsy surgery were included in the study. The epileptogenic zone was located in temporo-parieto-occipital areas as assessed by both invasive and non-invasive pre-surgical evaluation. Several variables (age at first seizure; age at surgery; disease duration; type, frequency and clinical semiology of seizures; presence of lesion; scalp ictal and interictal EEG; localization and extension of epileptogenic zone; completeness of surgical resection) were compared (Fisher's exact test) with freedom from seizures to determine whether surgical outcome (Engel's classification) could be related to any of them. RESULTS: Seven patients were seizure free (Ia) and very satisfying results were obtained for 3 patients (2 Ib, 1 Ic). New post-surgical visual deficits occurred only in 3 patients. Surgical outcome was related significantly to two variables: scalp ictal EEG (focal versus non-focal; p: 0.014) and completeness of surgical resection of epileptogenic zone (p: 0.0023). A significant trend towards a better outcome for focal interictal intracranial activity versus a non-focal one (p: 0.07) was found. CONCLUSIONS: The correlation between completeness of epileptogenic zone resection and surgical outcome suggests that a presurgical protocol, allowing a precise definition of the area of resection, could help in obtaining more satisfying results in posterior epilepsies.

Effects of vagus nerve stimulation on cortical excitability in epileptic patients.

Vagus nerve stimulation (VNS) is used as adjunctive treatment for medically refractory epilepsy, but little is known about its mechanisms of action. The effects of VNS on the excitatory and inhibitory circuits of the motor cortex were evaluated in five patients with epilepsy using single- and paired-pulse transcranial magnetic stimulation (TMS). Patients were examined with the stimulator on and off. VNS determined a selective and pronounced increase in the inhibition produced by paired-pulse TMS with no effects on the excitability by single-pulse TMS.

Comparison of descending volleys evoked by transcranial and epidural motor cortex stimulation in a conscious patient with bulbar pain.

OBJECTIVE: To compare the pattern of activation of motor cortex produced by transcranial magnetic stimulation and epidural electrical stimulation. METHODS: The spinal volleys evoked by transcranial magnetic stimulation and epidural electrical stimulation over the cerebral motor cortex were recorded from an electrode inserted into the cervical epidural space of one conscious subject who also had a cortical epidural electrode over the motor area. The volleys were termed D- and I-waves according to their latency. Magnetic stimulation was performed with a figure-of-eight coil and the induced current flowed either in a postero-anterior (PA) or in latero-medial (LM) direction. RESULTS: At active motor threshold intensity LM magnetic stimulation evoked a D wave whereas PA stimulation evoked an I(1) wave with later I waves being recruited at increasing stimulus intensities. Electrical epidural stimulation evoked both a D wave and I waves. However, the D wave evoked by electrical epidural stimulation had a longer latency than the LM D wave, suggesting either a more proximal site of activation of the pyramidal axon or activation of slightly faster conducting set of corticospinal fibres by LM stimulation. The I3 wave evoked by electrical epidural stimulation also had a longer latency than the PA I3-wave CONCLUSIONS: Epidural stimulation of the motor cortex can produce repetitive excitation of corticospinal neurones. The order of recruitment of the volleys, and the latency of the D and I3 waves may be slightly different to that seen after transcranial magnetic stimulation. SIGNIFICANCE: Our findings suggest that there may be subtle differences in the populations of neurones activated by the two forms of stimulation.

Direct recording of the output of the motor cortex produced by transcranial magnetic stimulation in a patient with cerebral cortex atrophy.

OBJECTIVE: To examine the descending motor activity evoked by transcranial magnetic stimulation (TMS) in a chronic alcoholic patient with a slight atrophy of the peri-central cortex and compare with that observed in neurologically intact subjects. METHODS: EMGs from the first dorsal interosseous (FDI) muscle, and descending activity from an electrode implanted in the high cervical epidural space for relief of pain were recorded after TMS of the hand area of motor cortex. A figure-of-8 coil was used to induce either a posterior-anterior (PA) or a latero-medial (LM) flow across the central sulcus. RESULTS: In intact subjects, LM stimulation evoked the earliest volley, which we termed a D wave. This was followed by later, presumed I waves at intervals of about 1.5 ms. At a stimulus intensity of 120% resting threshold (RMT), up to 5 I waves were seen. PA stimulation rarely evoked D waves at intensities up to 120% RMT, but 3 or 4 I waves were visible in all subjects. The patient had an increased resting threshold, and the descending volleys were dominated by a D wave. I waves were unclear, with two possible small peaks at 5.5 and 7.2 ms. CONCLUSIONS: The lack of I waves in the patient was probably due to an impairment of interneuronal circuitry in the context of the brain damage related to chronic alcohol abuse, and is consistent with a trans-synaptic origin of the I waves in humans. The intact D wave is consistent with the assumption that the D wave represents direct stimulation of the axons of intact corticospinal neurones in the subcortical white matter. The patient's increased RMT reflects the fact that usually multiple descending volleys are needed to discharge resting spinal motoneurones.

Subacute clinical onset of postraumatic myelopathy.

BACKGROUND: Subacute neurological deterioration unrelated to mechanical instability is a rare event. CASES REPORT: The authors describe two patients with subacute neurological deterioration unrelated to mechanical instability, which occurred 24 hours after spinal cord injury.The phenomenon could not be prevented by steroid therapy carried out either before or after the onset of clinical signs. An early surgical decompressive procedure performed in one of the two patients, failed to reverse the clinical symptomatology. FINDINGS: In the first case, temporal evolution of the neurological deterioration suggested a venous thrombosis with secondary congestive ischemia, whereas ischemia involving the anterior spinal artery seems to account for the deterioration observed in the second patient. INTERPRETATION: Spinal cord haemodynamics plays the main role in mediating the onset of descending subacute posttraumatic myelopathy. The cure and the prevention of the secondary vascular injury still remains unknown.

Craniocervical junction instability: instrumentation and fusion with titanium rods and sublaminar wires. Effectiveness and failures in personal experience.

BACKGROUND: The aim of the study was to evaluate the effectiveness, pitfalls and failures of instrumentation and fusion with titanium wires and rods in 12 h patients with craniovertebral junction instability. METHODS: Among nine adult patients (mean age 48.11 years) with craniovertebral junction instability, four had basilar impression, three metastatic disease, one rheumatoid arthritis and one Down's syndrome. Three children (mean age 7.33 years) with genetic (Down's syndrome, 2 cases) and metabolic (mucopolisaccarydoses type IV, i.e. Morquio Syndrome, 1 case) disease were studied as well. Each patient underwent preoperative radiological evaluation by means of X-Ray, CT scan and MRI of the craniocervical region. Occipitocervical instrumentation with a titanium U-shaped wired rod was performed in each patient. Autologous bone fusion was performed in all but the two cancer patients, in whom polymethylmetacrylate was used. Postoperatively, all the patients used an external orthosis for 3-6 months. Post-operative X-Ray, CT and MRI were performed on each patient. The Frankel clinical scale was used to asses the outcome at follow-up which ranged from 1 to 10 years. At maximum follow up, there was either clinical improvement or stabilization recorded in all but one patient. This patient with basilar impression transiently worsened from grade D to C and a spinal cord lesion was already evident before the operation on MRI examination. INTERPRETATION: The effectiveness of surgical management of craniovertebral junction instability by instrumentation and fusion was demonstratedly in our experience. Nevertheless, the choice of the surgical technique should be made with caution when a spinal cord lesion is revealed by preoperative neuroimaging studies.

Hypoflow and hyperflow in diffuse axonal injury. Prognostic and therapeutic implications of transcranial Doppler sonography evaluation.

BACKGROUND: In the present report we describe the results of a study aimed at evaluating the cerebral haemodynamics and the neuroradiological findings observ-ed in 7 consecutive patients, 4 adults and 3 children (6, 8 and 10 years old), affected by diffuse axonal injury (DAI). METHODS: All the patients were admitted to the Paediatric or Adult Intensive Care Unit with GCS scores less than 8 after a severe brain injury. Serial head CT scan and trans-cranial Doppler sonography (TCD) examinations were carried out in all patients; MRI was carried out in the paediatric patients only. TCD of the middle cerebral arteries was performed through the temporal bone window. In 6 cases (2 paediatric) diuretic osmotic therapy was immediately administered and in 6 cases (3 paediatric) barbiturates and hyperventilation were also used. RESULTS: Hyperflow, variably responsive to barbiturate therapy of vasoparalysis, was observed in all paediatric patients and in 3 adult subjects (85.7%: 6 out of 7 pa-tients) by means of TCD. CONCLUSIONS: Observation of these phenomena allowed us to modify the pharmacological treatment and/or perform external cerebrospinal fluid (CSF) drainage (4 cases). Compartimental hyperflow TCD pattern was evident in 1 patient. Although the limited number of patients in our series does not allow definitive conclusions, we strongly believe that TCD monitoring is an useful tool in planning surgical strategy in patients with DAI.

Descending spinal cord volleys evoked by transcranial magnetic and electrical stimulation of the motor cortex leg area in conscious humans.

1. Descending corticospinal volleys evoked after transcranial magnetic or electrical stimulation of the leg area of the motor cortex were recorded from an electrode in the spinal epidural space of six conscious patients who had electrodes implanted for treatment of chronic pain, and from one anaesthetised patient undergoing surgery for a spinal tumour. 2. At threshold, the shortest-latency volley (L1 volley) was evoked by stimulation with an anode 2 cm lateral to the vertex. Anodal stimulation at the vertex also elicited a volley at this latency in two patients, but in the other patients the first volley evoked appeared 1-1.3 ms later (L2 volley), at the same latency as the initial volley evoked by magnetic stimulation. High-intensity stimulation of any type could evoke both the L1 and L2 waves as well as later ones (L3, L4, etc.) that had a periodicity of about 1.5 ms. 3. Voluntary contraction increased the amplitude of the L2 and later volleys, but had no effect on the L1 volley. 4. Intracortical inhibition between pairs of magnetic stimuli resulted in clear suppression of the L4 and later waves. The L2 and L3 waves were unaffected. 5. In the anaesthetised patient the L1 volley occurred 1.7 ms later than the volley produced by transmastoid stimulation of the corticospinal pathways in the brainstem. 6. The L1 volley is likely to be a D wave produced by the direct activation of pyramidal axons in the subcortical white matter; the L2 and later volleys are likely to be I waves produced by the trans-synaptic activation of corticospinal neurones. The implication is that electrical stimulation with an anode at the vertex is more likely to evoke I waves preferentially than stimulation over the hand area. A more secure way to ensure D wave activation of corticospinal fibres from the leg area is to place the anode 2 cm lateral to the vertex.

Alternative technique for subclavian vein cannulation.

BACKGROUND: Subclavian vein catheterism, a commonly used methodology in ICU, is not devoid of complications, even some serious ones (Pneumothorax 0.5%). METHODS: The authors propose an alternative technique based on the use of an introducer needle bent on its own axis to form an arch with its concavity turned towards the Quincke point. On searching the blood vessel, once the subclavian plane has been reached, the needle advancement towards the jugular fosse happens by following the needle curvature. In this way the operator can keep the needle on a plane parallel to the cutaneous one, and all the complications due to involuntary exceeding of the costal plane are avoided. The response of this new technique in 110 patients (study group) is compared through a retrospective study, to 100 patients with whom the standard technique has been used (control group). RESULTS: The study group has presented a significant reduction both of total complications (p<0.05) and of total failures (p< 0.01). CONCLUSIONS: Such results, although pertinent to a still limited study, testify to an improvement in terms of security and efficacy, with the new alternative technique without an increase in costs.

Spinal cord stimulation and early experimental cerebral spasm: the "functional monitoring" and the "preventing effect".

BACKGROUND: Clinical and experimental data on cerebral blood flow (CBF) changes during spinal cord stimulation (SCS) were published since 1986. The aims of the present work are: 1. To find an experimental model of reliable, simple and in vivo monitoring of "early" basilar artery spasm after subarachnoid haemorrhage (SAH) and 2. To investigate the effects of cervical spinal cord stimulation (CSCS) on it. Vasospasm due to SAH is both "acute" and "recurrent". Early spasm occurs within minutes of the SAH. its duration is approximately 1 hour. The need of different morphological and haemodynamic methods to evaluate experimental early spasm is reported. To overcome intracranial surgical manipulations and biological effects of contrast and fixation media we designed a model that allows "in vivo" functional monitoring of basilar blood flow far away from the spasm without direct surgical and chemical interference. Subsequently we investigated the effects of CSCS on the new model of "functional monitoring" of the "early" cerebral vasospasm. METHOD: 29 adult Burgundy rabbits were studied. Group 1: under homeostatic monitoring, "on-line" carotid blood flow (carotid BF) changes produced by SAH in cisterna magna of 12 (plus 5 sham treated) animals were studied from the common carotid artery after external carotid artery occlusion before, during SAH and up to the end of the experiments. All the animals underwent digital subtraction cerebral panangiography (CPA) after SAH obtaining a significant increase of carotid BF only when basilar vasospasm was shown by CPA. Carotid BF increase during basilar vasospasm was defined "functional monitoring" of early spasm. Group 2: Twelve animals wearing a cervical epidural electrode underwent carotid BF "functional monitoring" of early basilar spasm before and during CSCS. FINDINGS: Carotid BF changes during CSCS occurred in 10 animals. No carotid BF changes (i.e. no basilar vasospasm) occurred after SAH up to the end of the experiments in all the stimulated animals. INTERPRETATION: CSCS is able to prevent "early spasm" due to SAH in all the animals studied with the new model of "functional monitoring" described, independently from the occurence and the sign for stimulation-induced carotid BF variations. The role and the limits of reversible functional sympathectomy in mediating the effect of CSCS on early vasospam are discussed.

FMRFamide in the amphibian brain: a comprehensive survey.

Mapping of FMRFamidergic neural circuitry in the amphibian brain has been done by immunohistochemical methods. Comparative evidence suggests that there are similarities and differences in the overall pattern of distribution of FMRFamide-ir elements in the brain among the three amphibian orders and within each order. FMRFamide is expressed in neurons in some circumscribed areas of the brain. A part of these neurons is concentrated in classical neurosecretory areas of the hypothalamus in a bilaterally symmetrical fashion. Similar neurons occur occasionally in the midbrain, but are virtually absent from the hindbrain. Anurans are unique among amphibians to show FMRFamide neurons in the medial septum and diagonal band of Broca. A viviparous gymnophione is known to possess a small population of such neurons in the dorsal thalamus. Together, the FMRFamide neurons contribute to an extensive fiber network throughout the amphibian brain. Descriptive developmental studies suggest that the rostral forebrain-located FMRFamide neurons originate in the olfactory placode and then migrate into the brain along the route of the vomeronasal-olfactory-terminal nerve complex. Olfactory placodal ablation in an anuran and a urodele provide experimental support to this contention. Other FMRFamide neuronal cell groups, in the hypothalamus and dorsal thalamus, are supposed to arise from non-placodal precursors. The neuroanatomical distribution (projection of immunoreactive processes to areas of the fore-, mid-, and hindbrain as well as to cerebrospinal fluid, co-localization with other neuropeptides, and presence in the median eminence) has furnished morphological correlates of possible functions of FMRFamide in the amphibian CNS. While amphibian FMRFamide-like or structurally related peptides remain to be isolated and characterized, the sum of the distribution pattern of FMRFamide-like immunoreactivity suggests that it may act as a neurotransmitter or a neuromodulator, and also may have endocrine regulatory functions.

Development and distribution of FMRFamide-like immunoreactivity in the toad (Bufo bufo) brain.

By using immunohistochemistry, we studied the development and distribution of the FMRFamide-like immunoreactive (ir) neuronal system in the toad brain during the ontogeny. In addition to this, experimental evidence was provided to show that the rostral forebrain-located FMRFamide neurons originate in the olfactory placode and then migrate into the brain along the olfactory pathway. During early development, within the brain, FMRFamide-ir perikarya first appeared in the periventricular hypothalamus. Later in development, FMRFamide-ir cells were visualized in the rostralmost forebrain simultaneously with similar ir cells in the developing olfactory mucosa. Selective ablation of the olfactory placode(s), prior to the appearance of the first FMRFamide-ir cells in the brain, resulted in the total absence of ir cells in the telencephalon (medial septum and mediobasal telencephalon) of the operated sides(s). The preoptic-suprachiasmatic-infundibular hypothalamus-located FMRFamide-ir neurons were not affected by olfactory placodectomy, arguing that they do not originate in the placode. This result points to the placode as the sole source of such neurons in the rostral forebrain.