[Central nervous system neuromodulation for the treatment of epilepsy. II. Mechanisms of action and perspectives]. / Neuromodulation du système nerveux central dans le traitement des épilepsies. II . Mécanismes d'action et perspectives.

OBJECTIVES: Review of available evidence of the mechanisms of action underlying the anticonvulsant effect of current applied to various CNS structures. MATERIAL AND METHODS: Studies were conducted from observations of patients with drug-resistant seizures and treated with neuromodulation. Seizures originated from various cortical areas with secondary generalization or were initially generalized without a focal origin, either clinically or on EEG or SEEG. Intracranial recordings and SEEG were performed using subdural grids or depth electrodes implanted either for recordings or therapeutic deep brain stimulation (DBS). In a group of mesial temporal lobe epilepsy patients investigated with subdural or SEEG electrodes, the epileptogenic focus area was stimulated for 15 days before anterior temporal lobectomy. The surgical specimen was examined using standard and electronic microscopy and autoradiography in order to identify several neurotransmitter receptors. They also were compared to other surgical specimens from epileptic patients who had intracerebral recordings but without stimulation (epileptic controls) and to autopsy specimens from subjects with no history of epilepsy (nonepileptic controls). RESULTS: High-frequency (HF) stimulation increases the after-discharge threshold of the stimulated site and alters the cycles of potentials evoked by a test stimulation using a paradigm of coupled stimulations. HF stimulation also decreases local cerebral blood flow in the stimulated area as demonstrated on SPECT. Parahippocampal cortex HF stimulation significantly increases the GABAergic benzodiazepine receptor density in the stimulated area. In addition, centromedianum (CM) thalamic nucleus HF stimulation suppresses thalamic and cortical spike-waves, as well as secondary synchronous discharges visible on EEG. Conversely, low-frequency (3-Hz) bilateral CM stimulation induces a typical absence clinically and on EEG. CONCLUSION: High-frequency stimulation is responsible for an inhibition of local and propagated epileptogenesis. Low-frequency stimulation may trigger or enhance epileptogenesis when applied on epileptogenic regions.

[Central nervous system neuromodulation for the treatment of epilepsy]. / Neuromodulation du système nerveux central dans le traitement des épilepsies I-Efficacité et sécurité de la méthode.

We present here a review of the work on neuromodulation - defined as application of an inhibitory or excitatory current - on intracranial structures for the treatment of drug-resistant epilepsy. Near 250 patients were treated using a neuromodulation technique of the cerebellum (paravermian cortex), the CM-pf nucleus of the thalamus, the hippocampus, epileptogenic foci, and anterior ventral nucleus of the thalamus, with a one- to 15-year follow-up. Four contact strips were used for cerebellar and functional region neuromodulation, and DBS-type depth electrodes were stereotactically implanted for CM-pf and anterior nuclei of the thalamus and hippocampal neuromodulation. Electric stimulation was cyclic in almost all trials, using low frequency (10-40 Hz) for excitation and high frequency (60-185 Hz) for inhibition. Seizure frequency reduction was variable, depending on the neuromodulation site and patient selection, although seizure duration decreased in most patients. Cerebellar neuromodulation was followed by a 78% reduction in tonic and tonic-clonic seizures, CM-pf neuromodulation by an 83% reduction in tonic-clonic seizures and atypical absence of Lennox-Gastaut syndrome, with a 17.2% seizure-free and drug-free patient rate. Hippocampal neuromodulation was followed by a 73% reduction in partial complex seizures, with a 33% seizure-free patient rate. Anterior ventral nucleus of the thalamus was followed by a 63% reduction in tonic-clonic, tonic and atonic seizures. Several prognostic factors were identified in order to improve future results. There was no mortality and morbidity was limited to skin erosion at the neurostimulator site. Seizure reduction was associated with improved neuropsychological performance and better quality of life. Neuromodulation is safe and effective for the treatment of epileptic seizures of various origins. Several targets may be associated in a single patient, especially when bilateral hippocampal seizure foci are present.

Neuromodulation of prelemniscal radiations in the treatment of Parkinson's disease.

In patients with Parkinson's disease (PD), tetrapolar electrodes were implanted in the prelemniscal radiations (RAPRL) to treat tremor, rigidity and bradykinesia. Fifteen patients were implanted unilaterally and five patients bilaterally and followed-up for one year. The selection criteria included the presence of unilateral pronounced tremor and rigidity in patients implanted unilaterally or bilateral symptoms including severe bradykinesia in patients implanted bilaterally. In the operating room, the tremor decreased significantly or was abolished following the insertion of the electrode in the RAPRL. This effect was temporary and subsided when the stimulation was off. However, when the stimulator was turned on, the severity of the symptoms and signs decreased significantly. The post-implantation MRI confirmed that the electrode contacts used for stimulation were inserted in RAPRL, a group of fibers located between the red nucleus and subthalamic nucleus, above the substantia nigra, medially to the zona incerta and below the thalamus. The patients were evaluated using the UPDRS part III, before implantation and every 3 months during the first year. Global scores decreased significantly. The pre- and postoperative median values (range in round brackets) were as follows: tremor improved from 3 (2-16) to 1 (2-3) (p<0.001); rigidity was either abolished or decreased markedly from 2 (1-16) to 0 (0-4) (p< 0.001); bradykinesia improved from 2 (0-4) to 1 (0-2) (p<0.001). We conclude that RAPRL, an area anatomically different from STN, is a good target for electrical stimulation in order to treat effectively all the main symptoms of PD.

The role of neuromodulation of the hippocampus in the treatment of intractable complex partial seizures of the temporal lobe.

We present the results of chronic electrical stimulation of the hippocampus (ESH) in 9 patients with complex partial seizures and at least 18 months follow-up. The magnetic resonance imaging (MRI) scan was normal in 5 while in 4 patients it showed hippocampal sclerosis. The seizure frequency ranged from 10 to 50 seizures per month. All patients were submitted to implantation of diagnostic 8-contact bilateral hippocampal depth electrodes to determine the location of epileptic foci. Once the focus was located, the diagnostic electrodes were replaced by deep brain stimulation (DBS) electrodes. Following DBS, all patients improved. With respect to outcome, patients were divided in two groups, one seizure-free (5 patients) and the other with residual seizures (4 patients). Both groups shared similar clinical features. However, the patients who were seizure free had normal MRI scan while those who had residual seizures were being stimulated on a sclerotic hippocampus. We conclude that electrical stimulation of the epileptic hippocampal formation can control mesial temporal seizures. Best results are obtained if we stimulate a hippocampus which does not show sclerosis in the MRI. In these cases, seizures are stopped and the recent memory tests improve even in patients with bilateral foci. This result is of extreme importance to patients who have either intractable seizures and normal MRI or bilateral epileptogenic foci, are excluded as candidates for temporal lobectomy and are left with no other alternative.

Deep brain stimulation for treatment of the epilepsies: the centromedian thalamic target.

Electrical stimulation (ES) of the thalamic centromedian nucleus (CMN) has been proposed as a minimally invasive alternative for the treatment of difficult-to-control seizures of multifocal origin and seizures that are generalized from the onset. ES intends to interfere with seizure propagation in a non-specific manner through the thalamic system. By adopting a frontal parasagittal approach and based on anterior-posterior (AC-PC) commissure intersection, deep brain stimulation (DBS) electrodes are stereotactically inserted. Electrophysiologic confirmation of electrodes position is accomplished by eliciting cortical recruiting responses and direct current (DC) shifts by low- and high-frequency stimulation through the electrodes. Cycling mode of bipolar stimulation has been used at 60-130 Hz, 0.45 msec, 2.5-3.5 V, 1 min ON in one side 4 min OFF, 1 min ON in the other side and 4 min OFF forward and back for 24h. ES of CMN significantly decreases generalized seizures of cortical origin and focal motor seizures. Best results are obtained in non-focal generalized tonic clonic seizures and atypical absences of the Lennox-Gastaut syndrome. Experience has indicated that the most effective target for seizure control is the thalamic parvocellular centromedian subnucleus.

Neuromodulation of the inferior thalamic peduncle for major depression and obsessive compulsive disorder.

Neuromodulation of the inferior thalamic peduncle is a new surgical treatment for major depression and obsessive-compulsive disorder. The inferior thalamic peduncle is a bundle of fibers connecting the orbito-frontal cortex with the non-specific thalamic system in a small area behind the fornix and anterior to the polar reticular thalamic nucleus. Electrical stimulation elicits characteristic frontal cortical responses (recruiting responses and direct current (DC)-shift) that confirm correct localization of this anatomical structure. A female with depression for 23 years and a male with obsessive-compulsive disorder for 9 years had stereotactic implantation of electrodes in the inferior thalamic peduncle and were evaluated over a long-term period. Initial OFF stimulation period (1 month) showed no consistent changes in the Hamilton Depression Scale (HAM-D), Yale Brown Obsessive Compulsive Scale (YBOCS), or Global Assessment of Functioning scale (GAF). The ON stimulation period (3-5 V, 130-Hz frequency, 450-msec pulse width in a continuous program) showed significant decrease in depression, obsession, and compulsion symptoms. GAF improved significantly in both cases. The neuropsychological tests battery showed no significant changes except from a reduction in the perseverative response of the obsessive-compulsive patient and better performance in manual praxias of the female depressive patient. Moderate increase in weight (5 kg on average) was observed in both cases.

On the confirmation of an effect of magnetic fields on the interictal firing rate of epileptic patients.

The effect of magnetic fields on interictal firing rates was investigated in three epileptic patients with depth electrode implantation in the hippocampus for pre-surgical evaluation. The protocol consisted of 10 min test periods, during which magnetic fields were cycled for 1 min on and 1 min off, and intervening 5 min rest periods. Only one patient revealed a 95% significant increase in the 10 s after the fields were switched on compared with the background estimate from the 10s before the fields were applied. This patient was also the only patient to show significant increases in firing rates during field-on compared with field-off periods, and during magnetic field test periods compared with intervening rest periods. This patient had a right hippocampal seizure onset. All patients showed increased firing rates during the 10 min periods of magnetic field testing compared to the 5 min rest periods between tests. This result was significant for the group at the 99% level. Two patients with right temporal lobe onset showed greater activity in the right hippocampus than the left. All patients exhibited a progressive increase in firing rates in rest periods between tests.

Predictors in the treatment of difficult-to-control seizures by electrical stimulation of the centromedian thalamic nucleus.

OBJECTIVE: To evaluate the efficacy of chronic electrical stimulation of centromedian thalamic nuclei (ESCM) in the treatment of difficult-to-control seizures. METHODS: Thirteen patients underwent ESCM for periods ranging from 12 to 94 months (mean, 41.2 mo) with electrodes stereotactically placed in both centromedian nuclei and connected to internalized stimulation systems. Electrode placement was guided by ventriculography and confirmed with magnetic resonance imaging before stimulation systems were internalized. Anatomic and electrophysiological confirmation of the electrodes' position was accomplished by plotting electrode position on anatomic sections of Schaltenbrand and Bailey's atlas, and testing cortical recruiting responses and electroencephalogram desynchronization elicited by acute low- or high-frequency stimulation, respectively. RESULTS: Improvement was highly significant for generalized tonicoclonic seizures and atypical absences. Better results were obtained for Lennox-Gastaut syndrome. These results were accompanied by a significant decrease in generalized spike-wave and secondary synchronous discharges, as well as focal spikes in the frontal regions. In contrast, ESCM reduced neither complex partial seizures nor focal spikes in temporal regions. Outcomes using ESCM for generalized epilepsy were better in patients in whom anatomic and electrophysiological confirmation of electrode placement was correct than in those in whom the target was missed bilaterally (P < 0.001). The effect was sustained during the observation period and was better for longer-term than for shorter-term stimulation periods. CONCLUSION: ESCM is an efficient and safe procedure for controlling certain seizure types, if patient selection and stereotactic placement are satisfactory.

Electrical stimulation of the prelemniscal radiation in the treatment of Parkinson's disease: an old target revised with new techniques.

OBJECTIVE: In the treatment of tremor and rigidity in patients with Parkinson's disease (PD), the prelemniscal radiation (RAPRL), a subthalamic bundle of fibers, is an exquisite target that can be visualized easily on ventriculograms. We sought to evaluate the effect of electrical stimulation of the RAPRL on symptoms and signs of PD in a long-term trial and to determine the localization of the stimulated area by means of stereotactic magnetic resonance imaging studies. METHODS: Ten patients with PD predominantly on one side had tetrapolar electrodes stereotactically oriented through a frontal parasagittal approach to the RAPRL contralateral to the most prominent symptoms. Preoperative and postoperative evaluations at 3, 6, 9, and 12 months after surgery were performed using conventional PD scales and quantitative evaluations of tremor amplitude and reaction time. Stereotactic high-resolution magnetic resonance imaging studies with the electrodes in place were used for anatomic localization. RESULTS: In all patients, temporary suppression of tremor occurred when the electrodes reached the target. The most effective stimulation was obtained when the pair of contacts was placed in the RAPRL. Long-term stimulation at 130 Hz, 0.09 to 0.450 milliseconds, and 1.5 to 3.0 V produced significant improvement in tremor and rigidity and mild improvement in bradykinesia. CONCLUSION: The RAPRL is an effective target for the alleviation of tremor and rigidity in patients with PD by either lesioning or neuromodulation; however, neuromodulation has the advantage of not inducing an increase in bradykinesia. The stimulated area seems to be independent of the subthalamic nucleus.

Centromedian-thalamic and hippocampal electrical stimulation for the control of intractable epileptic seizures.

The following two different modulatory procedures to control intractable epileptic seizures are presented: (1) chronic electrical stimulation of the centromedian-thalamic nucleus (ESCM) for control of generalized tonic-clonic seizures and atypical absences, and (2) subacute hippocampal stimulation (SAHCS) and chronic hippocampal stimulation for control of nonlesional temporal lobe seizures. The ESCM antiepileptic effect seems to be the result of activation of a nonspecific reticulothalamocortical system responsible for generalized electrocortical responses (recruiting, desynchronization, negative direct current shifts, and three spike-wave complexes per second). The success of the ESCM procedure depends on the following predictor factors: case selection (primary and secondary tonic-clonic seizures and atypical absences of the Lennox Gastaut syndrome), ventriculographic and electrophysiologic definition of the optimal stereotactic targets (based on the anterior commissure, posterior commissure, and the vertical line perpendicular to the posterior commissure and electrocortical recruiting responses), periodic electrophysiologic monitoring of the reliability of ESCM in the absence of the patient's subjective sensations and with totally internalized subcutaneous stimulation systems (by recording scalp electrocortical recruiting, desynchronizing, and direct current responses), quantitative evaluation of clinical and EEG improvement, and analysis of the ON and OFF effects, taking into account a long-lasting (possibly plastic) effect of ESCM. SAHCS blocks clinical and EEG signs of temporal lobe epileptogenesis with no additional damage of the stimulated hippocampal tissue. Preliminary results suggest that this antiepileptic effect is, at least in part, the result of a physiologic inhibition of the stimulated hippocampal tissue, because after SAHCS the authors found the following: (1) increased threshold and decreased duration, propagation, and blockage of the clinical signs accompanied with the hippocampal afterdischarge; (2) flattening of the hippocampal-evoked response recovery cycles; (3) single photon emission computed tomographic hypoperfusion; and (4) increased concentration of benzodiazepine receptor binding at the stimulated hippocampal region. Chronic hippocampal stimulation persistently blocked temporal lobe epileptogenesis in one patient under open protocols during 24 months with no apparent additional alterations in recent memory.

Sleep-epilepsy interactions in patients with intractable generalized tonic seizures and depth electrodes in the centro median thalamic nucleus.

Sleep-epilepsy interactions were studied in ten patients with Lennox-Gastaut Syndrome (LGS) suffering intractable generalized tonic seizures associated with generalized ictal fast spikes and interictal slow spike-wave complexes, where electrodes were implanted in the centromedian thalamic nucleus (CM) as part of a neuroaugmentive procedure for seizure control. In these patients, continuous all night recordings according to International Guidelines were performed to quantitatively determine changes in sleep patterns produced by the epileptic condition and changes in ictal and interictal surface and CM EEG activities produced by sleep stages. LGS patients showed significantly longer wakefulness (W) and shorter slow wave sleep (SWS) II than normals. Patients with seizures during the night showed shorter latency and larger number of paradoxical sleep (PS) periods than those patients without seizures. Ictal and interictal spike-wave EEG activities appeared together in surface and CM regions during all sleep stages with a ratio SURFACE/CM almost equal to one and PS did not focalize ictal and interictal activities in thalamic or cortical regions. Occurrence and duration of "myoclonic" ictal EEG component and number of interictal spike-wave complexes were higher during SWSII while they were smaller during PS than during W.

Absolute and relative predictor values of some non-invasive and invasive studies for the outcome of anterior temporal lobectomy.

BACKGROUND: There is controversy in the literature regarding the strategy used to obtain better outcomes after performing an anterior temporal lobectomy (ATL). Some investigators prefer to reduce the risks and costs of the predictor studies despite the fact that the number of patients cured after ATL (no seizures with no medication) is relatively small. Other investigators prefer to attempt a total cure in all patients by using all available predictor studies regardless of risks and costs. The latter strategy was the aim of the present work. METHODS: The absolute (%) and relative (ratio differences) predictor values of non-invasive and invasive studies for the outcome 24 months post-ATL were determined on 22 patients suffering from intractable non-lesional temporal lobe epilepsy. RESULTS: Under these conditions, 11 (50%) patients had excellent outcomes (seizure-free, no medication), 8 ( 36%), good outcomes (only auras with medication), and 3 (13.6%), poor ou tcomes (1 with >70%-seizure reduction and two no changes in seizure frequency). Predictors of excellent (vs. poor outcome) include the following: complex partial seizures (CXP) alone or associated with secondary generalized tonic-clonic seizures; ictal motionless stare and postictal amnesia; abnormal bitemporal spikes (prominent ipsilateral to ATL) and secondary bilateral synchrony EEG activities; focal hippocampal ictal EEG activities, and the presence of focal anterior temporal delta EEG activity 3 months after ATL. Predictors of poor (vs. excellent) outcomes include the following: CXP associated with other generalized seizure types; CTS, MRI, and EEG extratemporal abnormalities, and generalized basotemporal ictal EEG activities and the presence of seizures and focal anterior temporal spikes 3 months after ATL. CONCLUSIONS: The present study corroborates that no single predictive study (including non-invasive MRI and invasive ictal EEG activity) is predictive of the success or failure of ATL. Rather, a concordant combination of non-invasive and invasive studies is more likely to be predictive of a high probability of success. The high efficiency of ATL (86% of patients seizure-free) was accomplished by using all available predictor studies.

Acute and chronic electrical stimulation of the centromedian thalamic nucleus: modulation of reticulo-cortical systems and predictor factors for generalized seizure control.

The present report recapitulates the clinical and electrophysiologic studies we have performed on patients with certain forms of medically intractable epilepsy to investigate the basic mechanisms and predictor factors for seizure control of the electrical stimulation of the thalamic centromedian nucleus (CM) procedure. Acute electrical stimulation of CM reveals that in humans, as in other animals, CM represents a thalamic relay of a reticulo-cortical system that participates crucially in wakefulness and attentive processes and in regulation of cortical excitability, as well as in the physiopathology of genuine generalized epileptic seizures. For example, unilateral, threshold, low-frequency (6/sec) stimulation of CM produced electrocortical incremental responses, while high-frequency (60/sec) stimulation of CM produced electroencephalogram (EEG) desynchronization and electronegative DC shifts with no behavioral counterparts. In contrast, combined suprathreshold low-frequency (3/sec) stimulation of CM on one side and of mesencephalic reticular stimulation on the other produced generalized spike-wave complex discharges accompanied by the symptoms of a typical absence attack, including motionless stare, eye blinking, and unresponsiveness of patients to a series of flashes under a simple response task. Chronic bilateral, threshold, high-frequency (60/sec) stimulation of CM significantly decreased the number of primary and secondary generalized tonic-clonic seizures and atypical absence attacks and the amount of interictal generalized EEG discharges in both. In addition, it improved the psychological performance of patients and normalized the EEG by increasing the frequency of background EEG activity. In contrast, chronic stimulation of CM reduced neither the number of complex partial seizures nor the epileptic EEG activities localized in the temporal region. Good outcomes of the chronic CM stimulation procedure were achieved depending on correct selection of patients and accuracy of ventriculographic stereotactic targets, as well as on periodic clinical and EEG evaluation and electrophysiologic monitoring of CM electrical stimulation reliability. However, the presence of 3- to 6-month long-lasting effects of CM stimulation made statistical evaluation of ON-OFF effects of CM stimulation under placebo, double-masked randomized experiments difficult.

Subacute and chronic electrical stimulation of the hippocampus on intractable temporal lobe seizures: preliminary report.

Recent animal experiments show that the application of an electrical stimulus to the amygdala or hippocampus following the kindling stimulus produced a significant and long-lasting suppressive effect on this experimental model of epilepsy. This is a preliminary report on the development of a surgical neuromodulatory procedure by chronic electrical stimulation of the hippocampus (CHCS) for control of intractable temporal lobe seizures in patients in whom anterior temporal lobectomy is not advisable, i.e., patients with bilateral temporal foci or a unilateral focus spreading to surrounding cerebral regions of the dominant hemisphere. This work was divided in two main consecutive stages. In the first stage, we demonstrated that subacute hippocampal stimulation (SAHCS) blocks intractable temporal lobe epileptogenesis with no additional damage to the stimulated tissue, and in a second stage, we attempt to demonstrate that CHCS may produce a sustained, long-lasting antiepileptic condition without additional undesirable effects on language and memory. In addition, taking advantage of this unique and ethically permissible situation, we attempt to determine whether or not the antiepileptic effects of SAHCS and CHCS are due to inhibition of the stimulation of hippocampal tissue by means of a number of electrophysiological, single photon computed tomography (SPECT) perfusion, and autoradiographic techniques.SAHCS during 3-4 weeks prior to anterior temporal lobectomy applied to a critical area located either at the anterior Pes hippocampus close to the amygdala or at the parahippocampal gyrus close to the entorhinal cortex abolished clinical seizures and significantly decreased the number of interictal spikes at focus after 5-6 days. Microscopy analysis of the stimulated tissue showed no evident histopathological differences between stimulated vs. non-stimulated hippocampal tissues. Additionally, CHCS persistently blocked temporal lobe epileptogenesis for 3-4 months with no apparent additional undesirable effects on short memory. Also, inhibition of the stimulated hippocampus seems to be one of the possible mechanisms underlying the beneficial antiepileptic effects of SAHCS and CHCS. This was revealed by increased threshold and decreased duration of the afterdischarges induced by hippocampal stimulation, flattening of the hippocampal-evoked response recovery cycles, SPECT hypoperfusion of the hippocampal region, and increased hippocampal benzodiazepine receptor binding. Future studies increasing the number and time of follow-up of patients under hippocampal stimulation are necessary before considering CHCS a reliable procedure for controlling intractable temporal lobe seizures.

Decreased immunogenicity of fetal kidneys: the role of passenger leukocytes.

Early in gestation, fetal rat kidneys are less immunogenic than in later fetal stages, and also less immunogenic than early-gestation fetal hepatic tissue. The purpose of this study was to test this observation in an allogeneic model, and to explore the basis of the decreased immunogenicity of early-gestation fetal kidneys. Kidneys were harvested from Fischer (FSH) fetal rats on the 15th, 17th, 18th, and 19th gestational day (GD), and then grafted under the kidney capsule of incompatible Wistar/Furth (W/F) adult male rats. Fetal hepatic tissue was harvested from 15th-GD FSH fetal rats, and then grafted under the kidney capsule of W/F adult male rats. Each recipient received either one kidney or a 3-mm piece of liver. Graft biopsies were obtained 10, 20, 30, and 40 days posttransplantation, and evaluated histologically. The severity of rejection was divided into three grades according to the degree of mononuclear infiltration and percentage of original fetal structures preserved. All fetal hepatic grafts were completely rejected (grade III) by the tenth posttransplantation day. In contrast, the degree of rejection of the kidneys was age-dependent. Fifteenth-GD kidneys showed a minimal or moderate degree of rejection (grade I or II) at 10, 20, and 30 days; however, 18th- and 19-GD kidneys were rejected (grade III) by the tenth post-transplantation day. To explore the basis for the decreased immunogenicity of 15th-GD kidneys, 20 adult W/F rats were divided into two groups. Each animal in the first group received one FSH 15th-GD kidney implanted under the kidney capsule.(ABSTRACT TRUNCATED AT 250 WORDS)

Paratesticular malignant mesothelioma associated with abdominoscrotal hydrocele.

This is the report of 14-year-old boy with a malignant mesothelioma of the tunica vaginalis contained in an abdominoscrotal hydrocele. A review of the literature shows that this aggressive tumor is very rare and has been reported only in adults.

Intraosseous infusion of fluids in the initial management of hypovolemic shock in young subjects.

Immediate aggressive fluid resuscitation of a child with life-threatening hemorrhagic shock provides the difference between life and death. Obtaining venous access in the hypovolemic child sometimes is difficult and time consuming. In order to evaluate the benefit of prehospital administration of intraosseous fluids into the tibial bone marrow as a method of gaining quick access to the systemic circulation and in resuscitating victims from severe hypovolemic shock, 13 puppies weighing 4.6 to 10 kg were subjected to progressive, controlled exsanguination until their mean arterial pressure (MAP) was 20% or less of their baseline MAP for 5 minutes (maxishock). Then an 18-gauge intraosseous needle was inserted into the tibial bone marrow and lactated Ringer's solution was infused at 300 mm Hg of pressure until a volume three times the blood loss had been administered. The MAP, central venous pressure, arterial blood gases, hematocrit, serum lactate, and urine output were recorded at 10, 20, 30, 45, 60, 90, and 120 minutes after the onset of maxishock. At the end of the experiment the left lung of each animal was sent to the pathology department to investigate the possibility of bone marrow emboli. The results were compared with a group of control dogs with maxishock and no treatment, and a group of dogs with maxishock treated with a canine military antishock trousers inflated to 50 to 55 mm Hg and no fluids. The average needle insertion time was 16 seconds; the rate of infusion of fluids varied from a maximum of 25.7 mL/min to a minimum of 4.5 mL/min, with a mean of 10.6 mL/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of congenital microgastria.

Congenital microgastria is a rare anomaly. Only 22 cases have been reported in the literature. Its clinical manifestations depend on the stage at which the embryologic development of the stomach is arrested. The outcome of most patients with severe microgastria previously reported has either been death or extreme malnutrition. Since 1978, four patients with congenital microgastria have been managed at The Children's Hospital of Philadelphia. All patients had severe feeding intolerance and associated congenital malformations. Three patients were treated with a double lumen Roux-en-Y jejunal reservoir (Hunt-Lawrence pouch). This treatment improved the nutritional management of these patients. On follow-up two patients are at the 50th percentile for height and weight, and one is at the 25th percentile. One patient with associated severe congenital heart disease was treated nonoperatively. Her nutritional management was difficult, and she ultimately died of congestive heart failure at 3 years of age. In patients with the most severe forms of microgastria, early operative treatment improves nutritional management and facilitates the achievement of normal growth and development.

Retroperitoneal fibrosis in a patient with Turner's syndrome.

Retroperitoneal fibrosis rarely affects children. Its clinical manifestations are protean, but if recognized early and properly treated, the prognosis is generally good. This is the report of a 14-year-old girl with Turner's syndrome and retroperitoneal fibrosis.

Effect of chronic electrical stimulation of the centromedian thalamic nuclei on various intractable seizure patterns: I. Clinical seizures and paroxysmal EEG activity.

Twenty-three patients with various intractable seizure patterns were divided into four groups based on their most frequent seizure type and their clinical and EEG response to chronic electrical stimulation of the centromedian thalamic nuclei (ESCM): group A, generalized tonic-clonic (GTC, n = 9); group B, partial motor (Rasmussen type) (n = 3); group C, complex partial seizures (CPS, n = 5); and group D, generalized tonic seizures (Lennox-Gastaut type) (n = 6). CM were radiologically and electrophysiologically localized by means of stereotaxic landmarks and by thalamically induced scalp recruiting-like responses and desynchronization. ESCM consisted of daily 2-h stimulation sessions for 3 months. Each stimulus consisted of a 1-min train of square pulses with a 4-min interstimulus interval, alternating right and left CM. Each pulse was 1.0 ms in duration at 60/s frequency and 8-15 V (400-1,250 microA) amplitude. Voltage (V), current flow (microA) and impedance (k omega) at the electrode tips were kept constant. A significant decrease in the number of seizures per month and paroxysmal EEG waves per 10-s spochs occurred in group A patients between the baseline period (BL) and the ESCM period. These changes persisted for > 3 months after discontinuation of ESCM (poststimulation period, Post). Post was accompanied by a significant decrease in the number of paroxysmal EEG discharges. A substantial decrease in seizures and paroxysmal discharges was also observed in patients of group B. In contrast, patients of groups C and D showed no significant changes from BL to ESCM and Post periods, except for a significant decrease in the number of seizures in group D patients from BL to Post periods.