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Biomedical subjects

J P Nguyen

Publications and source records attributed to J P Nguyen.

At least 19 recordsLinked to original sources
PubMed2006

Somatotopic organization of the analgesic effects of motor cortex rTMS in neuropathic pain.

BACKGROUND: Motor cortex repetitive transcranial magnetic stimulation (rTMS) was found to relieve chronic neuropathic pain, but the optimal parameters of stimulation remain to be determined, including the site of stimulation. OBJECTIVE: To determine the relationship between cortical stimulation site and pain site regarding the analgesic efficacy of rTMS of motor cortex in chronic neuropathic pain. METHODS: Thirty-six patients with unilateral chronic neuropathic pain located at the face or the hand were enrolled. Motor cortex rTMS was applied at 10 Hz over the area corresponding to the face, hand, or arm of the painful side, whatever pain location. Analgesic effects were daily assessed on visual analogue scale for the week that followed each rTMS session. RESULTS: All types of rTMS session, whatever the target, significantly relieved pain, compared with baseline. However, analgesic effects were significantly better after hand than face area stimulation in patients with facial pain and after face than hand or arm area stimulation in patients with hand pain. CONCLUSION: Repetitive transcranial magnetic stimulation was more effective for pain relief when the stimulation was applied to an area adjacent to the cortical representation of the painful zone rather than to the motor cortical area corresponding to the painful zone itself. This result contradicts the somatotopic efficacy observed for chronic epidural motor cortex stimulation with surgically implanted electrodes.

Adult↗
PubMed2006

Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain.

OBJECTIVE: To assess cortical excitability changes in patients with chronic neuropathic pain at baseline and after repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. METHODS: In 22 patients with unilateral hand pain of various neurologic origins and 22 age-matched healthy controls, we studied the following parameters of cortical excitability: motor threshold at rest, motor evoked potential amplitude ratio at two intensities, cortical silent period (CSP), and intracortical inhibition (ICI) and intracortical facilitation. We compared these parameters between healthy subjects and patients at baseline. We also studied excitability changes in the motor cortex corresponding to the painful hand of patients after active or sham rTMS of this cortical region at 1 or 10 Hz. RESULTS: At baseline, CSP was shortened for the both hemispheres of patients vs healthy subjects, in correlation with pain score, while ICI was reduced only for the motor cortex corresponding to the painful hand. Regarding rTMS effects, the single significant change was ICI increase in the motor cortex corresponding to the painful hand, after active 10-Hz rTMS, in correlation with pain relief. CONCLUSION: Chronic neuropathic pain was associated with motor cortex disinhibition, suggesting impaired GABAergic neurotransmission related to some aspects of pain or to underlying sensory or motor disturbances. The analgesic effects produced by motor cortex stimulation could result, at least partly, from the restoration of defective intracortical inhibitory processes.

Adult↗
PubMed2004

Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex.

Neuropathic pain can be controlled by motor cortex stimulation using surgically-implanted electrodes in a majority of selected patients. Analgesic effects were also found to result from repetitive transcranial magnetic stimulation (rTMS) of the cortex. We report the case of a woman, in whom drug-resistant peripheral pain was controlled for 16 months by monthly sessions of motor cortex rTMS until a durable pain relief was obtained after surgical implantation of a cortical stimulator. This case illustrates the value of rTMS in helping patients to wait for surgery.

Adult↗
PubMed2004

Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study.

Huntington's disease (HD) is a monogenic neurodegenerative disease that affects the efferent neurons of the striatum. The protracted evolution of the pathology over 15 to 20 years, after clinical onset in adulthood, underscores the potential of therapeutic tools that would aim at protecting striatal neurons. Proteins with neuroprotective effects in the adult brain have been identified, among them ciliary neurotrophic factor (CNTF), which protected striatal neurons in animal models of HD. Accordingly, we have carried out a phase I study evaluating the safety of intracerebral administration of this protein in subjects with HD, using a device formed by a semipermeable membrane encapsulating a BHK cell line engineered to synthesize CNTF. Six subjects with stage 1 or 2 HD had one capsule implanted into the right lateral ventricle; the capsule was retrieved and exchanged for a new one every 6 months, over a total period of 2 years. No sign of CNTF-induced toxicity was observed; however, depression occurred in three subjects after removal of the last capsule, which may have correlated with the lack of any future therapeutic option. All retrieved capsules were intact but contained variable numbers of surviving cells, and CNTF release was low in 13 of 24 cases. Improvements in electrophysiological results were observed, and were correlated with capsules releasing the largest amount of CNTF. This phase I study shows the safety, feasibility, and tolerability of this gene therapy procedure. Heterogeneous cell survival, however, stresses the need for improving the technique.

Animals↗
PubMed2003

Low levels of ventricular CSF orexin/hypocretin in advanced PD.

The origins of excessive daytime sleepiness in Parkinson disease (PD) are unclear. The authors hypothesize that orexin neurons, a recently identified wake promoting system, could contribute to its pathophysiology. They measured orexin-A/hypocretin-1 concentration in ventricular CSF in 19 parkinsonian patients and compared it with neurologic controls. Orexin levels were lower in patients and decreased with the severity of the disease. The authors suggest that orexin neurons contribute to daytime sleepiness in late stage PD.

Antiparkinson Agents↗
PubMed2001

Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex.

Chronic electrical stimulation of the precentral (motor) cortex using surgically implanted electrodes is performed to treat medication-resistant neurogenic pain. The goal of this placebo-controlled study was to obtain such antalgic effects by means of a non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS). Eighteen patients with intractable neurogenic pain of various origins were included and underwent a 20 min session of either 10 Hz, 0.5 Hz or* sham rTMS over the motor cortex in a random order. A significant decrease in the mean pain level of the series was obtained only after 10 Hz rTMS. This study shows that a transient pain relief can be induced by 10 Hz rTMS of the motor cortex in some patients suffering from chronic neurogenic pain.

Adult↗
PubMed2001

Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex.

The chronic electrical stimulation of a motor cortical area corresponding to a painful region of the body, by means of surgically-implanted epidural electrodes is a validated therapeutical strategy to control medication-resistant neurogenic pain. Repetitive transcranial magnetic stimulation (rTMS) permits to stimulate non-invasively and precisely the motor cortex. We applied a 20-min session of rTMS of the motor cortex at 10 Hz using a 'real' or a 'sham' coil in a series of 14 patients with intractable pain due to thalamic stroke or trigeminal neuropathy. We studied the effects of rTMS on pain level assessed on a 0-10 visual analogue scale from day 1 to day 12 following the rTMS session. A significant pain decrease was observed up to 8 days after the 'real' rTMS session. This study shows that a transient pain relief can be induced in patients suffering from chronic neurogenic pain during about the week that follows a 20-min session of 10 Hz-rTMS applied over the motor cortex.

Adult↗
PubMed2001

Chiari I malformation: a rare cause of noncommunicating hydrocephalus treated by third ventriculostomy.

OBJECT: Hydrocephalus associated with Chiari I malformation is a rare entity related to an obstruction in the flow of cerebrospinal fluid (CSF) in the foramen of Magendie. Like all forms of noncommunicating hydrocephalus. it can be treated by endoscopic third ventriculostomy (ETV). The object of this study is to report a series of five cases of hydrocephalus associated with Chiari I malformation and to evaluate the use of ETV in the treatment of this anomaly. METHODS: Five patients (four women and one man with a mean age of 29.6 years) underwent ETV for hydrocephalus associated with Chiari I malformation between April 1991 and February 1997. All patients had presented with paroxysmal headaches, which in two cases were associated with visual disorders. All patients had also presented with hydrocephalus (mean transverse diameter of the third ventricle 12.79 mm; mean sagittal diameter of the fourth ventricle 18.27 mm) with a mean herniation of the cerebellar tonsils at 13.75 mm below the basion-opisthion line. Surgery was performed in all patients by using a rigid endoscope. No complications occurred either during or after the procedure, except in one patient who experienced a wound infection that was treated by antibiotic medications. The mean duration of follow up in this study was 50.39 months. Four patients became completely asymptomatic and remained stable throughout the follow-up period. One patient required an additional third ventriculostomy after I year, due to secondary closure, and has remained stable since that time. Postoperative magnetic resonance images demonstrated a significant reduction in the extent of hydrocephalus in all patients (mean transverse diameter of the third ventricle 6.9 mm [p = 0.0035]; mean sagittal diameter of the fourth ventricle 10.32 mm [p = 0.007]), with a mean ascent of the cerebellar tonsils from 13.75 mm below the basion-opisthion line to 7.76 mm below it (p = 0.01). In addition, CSF flow was identified on either side of the orifice of the third ventriculostomy in all patients postoperatively. CONCLUSIONS: Results in this series confirm the efficacy of ETV in the treatment of hydrocephalus associated with Chiari I malformation. It is a reliable, minimally invasive technique that also provides a better understanding of the pathophysiology of this malformation.

Adult↗
PubMed2000

Motor and cognitive improvements in patients with Huntington's disease after neural transplantation.

BACKGROUND: Huntington's disease is a neurodegenerative disease of genetic origin that mainly affects the striatum. It has severe motor and cognitive consequences and, up to now, no treatment. Motor and cognitive functions can be restored in experimental animal models by means of intrastriatal transplantation of fetal striatal neuroblasts. We explored whether grafts of human fetal striatal tissue could survive and have detectable effects in five patients with mild to moderate Huntington's disease. METHODS: After 2 years of preoperative assessment, patients were grafted with human fetal neuroblasts into the right striatum then, after a year, the left striatum. Final results were assessed 1 year later on the basis of neurological, neuropsychological, neurophysiological, and psychiatric tests. The results obtained were compared with those of a cohort of 22 untreated patients at similar stages of the disease who were followed up in parallel. Repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning with fluorine-18-labelled fluorodeoxyglucose was also done to assess metabolic activity. FINDINGS: The final PET-scan assessment showed increased metabolic activity in various subnuclei of the striatum in three of five patients, contrasting with the progressive decline recorded in the two other patients in the series, as seen in patients with untreated Huntington's disease. Small areas of even higher metabolic activity, coregistering with spherical hyposignals on MRI were also present in the same three patients, suggesting that grafts were functional. Accordingly, motor and cognitive functions were improved or maintained within the normal range, and functional benefits were seen in daily-life activities in these three patients, but not in the other two. INTERPRETATION: Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with Huntington's disease.

Brain↗
PubMed2000

Neuroprotective gene therapy for Huntington's disease using a polymer encapsulated BHK cell line engineered to secrete human CNTF.

Huntington's disease (HD) is an autosomal dominant genetic disease with devastating clinical effects on cognitive, psychological, and motor functions. These clinical symptoms primarily relate to the progressive loss of medium-spiny GABA-ergic neurons of the striatum. There is no known treatment to date. Several neurotrophic factors have, however, demonstrated the capacity to protect striatal neurons in various experimental models of HD. This includes the ciliary neurotrophic factor (CNTF), the substance examined in this protocol. An ex vivo gene therapy approach based on encapsulated genetically modified BHK cells will be used for the continuous and long-term intracerebral delivery of CNTF. A device, containing up to 106 human CNTF-producing BHK cells surrounded by a semipermeable membrane, will be implanted into the right lateral ventricle of 6 patients. Capsules releasing 0.15-0.5 microg CNTF/day will be used. In this phase I study, the principal goal will be the evaluation of the safety and tolerability of the procedure. As a secondary goal, HD symptoms will be analyzed using a large battery of neuropsychological, motor, neurological, and neurophysiological tests and the striatal pathology monitored using MRI and PET-scan imaging. It is expected that the gene therapy approach described in this protocol will mitigate the side effects associated with the peripheral administration of recombinant hCNTF and allow a well-tolerated, continuous intracerebroventricular delivery of the neuroprotective factor.

Animals↗
PubMed2000

Safety and tolerability assessment of intrastriatal neural allografts in five patients with Huntington's disease.

This study describes issues related to the safety and tolerability of fetal striatal neural allografts as assessed in five patients with Huntington's disease. Huntington's disease (HD) is characterized by motor, cognitive, and behavioral disturbances. The latter include psychological disturbances and, as a consequence, we took particular care to analyze behavioral changes, in addition to the usual "safety" follow-up. We conducted multidisciplinary follow-up at least 2 years before and 1 year after grafting. Psychological care extended to close relatives. The grafting procedure itself was altogether safe and uneventful, and there were no apparent clinical deleterious effects for 1 year. The immunosuppressive treatment, however, was complicated by various problems (irregular compliance, errors of handling, side effects). Direct psychological consequences of the transplantation procedure were rare and not worrisome, although mood alteration requiring treatment was observed in one patient. Indirectly, however, the procedure required patients and relatives to accept constraints that tended to complicate familial situations already marred by aggressivity and depression. All patients and close relatives expressed major expectations, in spite of our strong and repeated cautioning. It is clearly important to be aware of these particular conditions since they may eventually translate into psychological difficulties in coping with the long-term clinical outcome of the procedure, if not beneficial. Despite an overall good tolerance, therefore, this follow-up calls for caution regarding the involvement of HD patients in experimental surgical protocols.

Adult↗
PubMed2000

Soleus neurotomy for treatment of the spastic equinus foot. Groupe d'Evaluation et de Traitement de la Spasticité et de la Dystonie.

OBJECTIVE: This prospective, nonrandomized, noncontrolled study was performed to evaluate the results of a new type of neurotomy, namely the soleus neurotomy, for treatment of the spastic equinus foot. METHODS: Between May 1996 and March 1998, 46 patients were treated for a spastic equinus foot. Clinical status, spasticity (Ashworth Scale score), and kinematic parameters of the gait were determined before and after surgery. The neurotomy was performed on the upper nerve of the soleus in all cases and was associated with other neurotomies (lower nerve of the soleus, 21 patients; gastrocnemius, 9 patients, tibialis posterior, 18 patients; flexor hallucis longus, 16 patients; and flexor digitorum longus, 17 patients). RESULTS: The mean follow-up period was 15 months (range, 8-28 mo). The equinus deformity disappeared clinically in all patients. Before the operation, all patients had an Ashworth Scale score of 2, with an inexhaustible clonus present on knee extension and persisting with knee flexion (Tardieu Scale score, 4), which was abolished in 95% of the patients after surgery. Two patients still had some clonus on knee extension; this did not interfere with their clinical improvement. Knee recurvatum disappeared in eight patients. Analysis of kinematic parameters demonstrated a statistically significant increase in joint motion of the second rocker (P = 0.0026) of the ankle during stance. The duration of the stance or swing phase, length of the walking cycle, and velocity or rate of spontaneous walking were not significantly modified. CONCLUSION: The study demonstrated that soleus neurotomy is effective for the treatment of spastic equinus foot, leading to abolition of spasticity and improvement in the range of ankle motion during the stance phase of gait.

Adolescent↗
PubMed2000

A new device for endoscopic third ventriculostomy.

Since its description by Dandy in 1922, several techniques have been used to perform third ventriculostomy under endoscopic control. Except for the blunt technique, in which the endoscope is used by itself to create the opening in the floor of the third ventricle, the other techniques require more than one instrument to perforate the floor of the ventricle and enlarge the ventriculostomy. The new device described is a sterilizable modified forceps that allows both the opening of the floor and the enlargement of the ventriculostomy in a simple and effective way. The new device has the following characteristics: 1) the tip of the forceps is thin enough to allow the easy perforation of the floor of the ventricle; 2) the inner surface of the jaws is smooth to avoid catching vessels of the basal cistern; and 3) the outer surface of the jaws has indentations that catch the edges of the opening to prevent them from slipping along the instrument's jaws. The ventricle floor is opened by gentle pressure of the forceps, which is slowly opened so that the edges of the aperture are caught by the distal outer indentation of the jaws, leading to an approximately 4-mm opening of the floor. This device has been used successfully in 10 consecutive patients. This new device allows surgeons to perform third ventriculostomy under endoscopic control in a very simple, quick, and effective way, avoiding the need for additional single-use instruments.

Endoscopes↗
PubMed2000

[Endoscopic anatomy of the third ventricle].

According to the development of neurosurgical endoscopy (and especially for third ventriculostomy), the endoscopic anatomy in hydrocephalus should be well known and utilized for orientation. The endoscopic pictures are obtained with a 30; telescope, acquired by a digitalized camera and visualized on a video monitor. The pictures are then numerized on a DKR system. Endoscopic anatomy of the third ventricle is described with a particular focus on the anatomical landmarks and their variations around the foramen of Monro, the anterior and posterior walls of the third ventricle. The knowledge of this anatomy is essential for the safety and the reliability of intraventricular endoscopic procedures.

Endoscopy↗
PubMed2000

[Treatment of central and neuropathic facial pain by chronic stimulation of the motor cortex: value of neuronavigation guidance systems for the localization of the motor cortex].

Thirty two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27. 3 months. The first 24 patients were operated according to the technique described by Tsubokawa. The last 13 cases (8 new patients and 5 reinterventions) were operated by a technique including localization by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organisation of the motor cortex was established peroperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and nine of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the 3 patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zoster. None of the patients developed epileptic seizures. The position of the stimulating poles effective on pain corresponded to the somatotopic representation of the motor cortex. The neuronavigator localization and guidance technique proved to be most useful identifying the appropriate portion of the motor gyrus. It also allowed the establishment of reliable correlations between electrophysiological-clinical and anatomical data which may be used to improve the clinical results and possibly to extend the indications of this technique.

Adult↗
PubMed1999

Cortical stimulation and epileptic seizure: a study of the potential risk in primates.

OBJECTIVE: The recent successful development of chronic stimulation of the motor cortex as a treatment for neuropathic and central pain does not exclude the possibility of eventual side effects, such as epileptic seizure or a lowering of the epileptic threshold. This study evaluates the behavioral and electroencephalographic impact of this treatment in three normal monkeys. RESULTS: None of the monkeys presented epileptic behavior or abnormal electroencephalographic activity at parameters of stimulation currently used in clinical series, i.e., frequency and pulse duration of approximately 40 Hz and 90 microseconds, respectively, and an intensity just under the threshold for inducing muscle twitch in painful areas. Higher intensities did, however, induce reversible epileptic seizure. There was, nonetheless, no modification of the epileptic threshold, because even after these seizures, intermittent light stimulation elicited no abnormal electroencephalographic activity. CONCLUSION: It thus seems that motor cortex stimulation does not induce epileptic complications when the classic clinical criteria of stimulation are respected. Nevertheless, it would be wise to subject candidates for implantation to intermittent light stimulation before and after a period of stimulation to ascertain the innocuousness of the cortical stimulation.

Animals↗
PubMed1998

Improvement of action tremor by chronic cortical stimulation.

The authors present a patient who had long-term improvement of a severe upper limb action tremor after chronic cortical stimulation. A 40-year-old woman complained of facial pain and tremor of the left arm after removal of an acoustic neurinoma. A motor cortex stimulation was performed to treat the deafferentation facial pain in 1993. Chronic cortical stimulation induced complete relief of both pain and tremor and allowed the patient to recover functional capacity of the limb. These effects persisted throughout a 32-month follow up. Differential effects on pain and tremor were observed when parameters of stimulation were varied, suggesting different mechanisms for the relief of pain and tremor. Attention was focused on control of the tremor. This effect could be the result of the inhibition of subcortical structures which are involved in tremor. Chronic cortical stimulation appears to be an effective treatment for controlling severe action tremors.

Activities of Daily Living↗