Fiacro Jiménez

A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle

OBJECTIVE AND IMPORTANCE: The present report explored the effect of electrical stimulation on the inferior thalamic peduncle in a patient with resistant major depression disorder (MDD). CLINICAL PRESENTATION: This report refers to a 49-year-old woman with a history of recurrent episodes of major depression for 20 years (12 episodes and 2 hospitalizations), fulfilling Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised, criteria for MDD; in addition, the patient met criteria for borderline personality disorder and bulimia. Her longest episode of depression with suicidal ideation began 5 years before surgery. The patient’s symptom array responded poorly to different combinations of antidepressants, cognitive therapy, and electroconvulsive therapy, which induced improvement only for short periods of time. Immediately before surgery, her Global Assessment of Functioning score was 20 and her Hamilton Depression Scale score ranged from 33 to 42. The patient was proposed for surgery for MDD. INTERVENTION: The patient had bilateral eight-contact electrodes stereotactically implanted for stimulation of areas at and around the inferior thalamic peduncle. Electrode position was corroborated by unilateral electrical stimulation searching for recruiting responses and regional direct current shifts in the electroencephalogram. Recording electrodes were replaced by tetrapolar electrodes for deep brain stimulation and connected to an internalized stimulation system for continuous bipolar stimulation at 130 Hz, 0.45 milliseconds, 2.5 V. Bimonthly follow-up included psychiatric and neuropsychological evaluations performed over the course of 24 months. After 8 months of ON stimulation, the patient entered a double-blind protocol with stimulators turned OFF. Improvement of depression measured by the Hamilton Depression Scale score was evident after initial placement of electrodes without electrical stimulation. Depression relapsed partially at the end of the first week. Electrical stimulation further improved depression, normalizing depression scores and neuropsychological performance. Patient depression scores ranked between 2 and 8 during 8 months of ON stimulation without antidepressant medication. After stimulation was turned OFF, spontaneous fluctuations in patient symptoms reflected by Hamilton Depression Scale and Global Assessment of Functioning scores were documented; these fluctuations disappeared after stimulation was turned on by Month 20. CONCLUSION: Complicated patients with comorbid conditions are common referrals to psychosurgery services. In this report, we present promising results of electrical stimulation of the inferior thalamic peduncle to treat recurrent unipolar depression in a patient with MDD and borderline personality disorder who responded poorly to treatment.

Electrical stimulation of the centromedian thalamic nucleus in control of seizures : long-term studies

Summary: Five patients with chronic incapacitating seizures averaging 15–5,000/month were selected for study. All patients had more than one seizure type and had received maximal doses of antiepileptic drugs (AEDs). The centromedian thalamic nucleus (CM) was stimulated electrically through bilateral multicontact platinum electrodes stereotaxically placed in CM and connected to internalized pulse generators. Electrophysiologic confirmation of electrode position included thalamically elicited recruiting responses and EEG desynchronization recorded at the scalp. Stimulation parameters were adjusted individually in the range of 450–800‐μA intensity, 65 pps, 0.09 ms, in 1‐min trains, alternating right and left side stimulation and with 4‐min intervals delivered for 2 h/day. Quantitative evaluation included frequency of seizures/month, number of maximal interictal paroxysmal discharges, and frequency of background activities counted in selected scalp EEG samples, taken throughout the observation period (7–33 months). Significance of changes was evaluated by parametric Students t test. Generalized tonic‐clonic seizures (GTC) decreased dramatically, almost disappearing in all cases (p < 0.001), with a significant reduction in interictal paroxysmal discharges (p < 0.01) and a tendency toward an increase in EEG back‐ground frequency. Other generalized seizures (atypical absences) decreased significantly, but there was no change in the number of complex partial seizures (CPS). CM stimulation is useful in control of GTC, but its beneficial effect on other seizure types has not been established.

Predictors in the Treatment of Difficult-to-control Seizures by Electrical Stimulation of the Centromedian Thalamic Nucleus

OBJECTIVEnTo evaluate the efficacy of chronic electrical stimulation of centromedian thalamic nuclei (ESCM) in the treatment of difficult-to-control seizures.nnnMETHODSnThirteen 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 Baileys atlas, and testing cortical recruiting responses and electroencephalogram desynchronization elicited by acute low- or high-frequency stimulation, respectively.nnnRESULTSnImprovement 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.nnnCONCLUSIONnESCM is an efficient and safe procedure for controlling certain seizure types, if patient selection and stereotactic placement are satisfactory.

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.

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 recruitinglike 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 μ‐A) amplitude. Voltage (V), current flow (μA) and impedance (kΩ) at the electrode tips were kept constant. A significant decrease in the number of seizures per month and paroxysmal EEG waves per 10‐s epochs 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.

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

OBJECTIVEIn 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. METHODSTen 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. RESULTSIn 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. CONCLUSIONThe 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.

Stimulation of the central median thalamic nucleus for epilepsy

Electrical stimulation of the centromedian thalamic nucleus (ESCM) has been used in cases of difficult to control seizures with multifocal onset in frontal and temporal lobes, as well as in cases of seizures with no evidence of focal onset, such as Lennox-Gastaut syndrome. The stimulation program consists of 1 min stimulation on one side, 4 min interval OFF stimulation and 1 min stimulation on the other side, alternating from one side to the other for 24 h, at 60–130 Hz, 2.5–5.0 V, 0.21–0.45 ms. 49 cases have been treated and followed for periods of 6 months to 15 years. Results indicate that ESCM is highly efficient to control generalized tonic clonic seizures (GTC), atypical absences (AA) and tonic seizures (TS) and less efficient to control complex partial seizures (CxP).

Neurobiological background for performing surgical intervention in the inferior thalamic peduncle for treatment of major depression disorders.

OBJECTIVE: To present a review of evidence for an inhibitory thalamo-orbitofrontal system related to physiopathology of major depression disorders (MDDs) and to postulate that interfering with hyperactivity of the thalamo-orbitofrontal system by means of chronic high-frequency electrical stimulation of its main fiber connection, the inferior thalamic peduncle (ITP), may result in an improvement in patients with MDD. METHODS: Experimentally, the thalamo-orbitofrontal system has been proposed as part of the nonspecific thalamic system. Under normal conditions, the nonspecific thalamic system induces characteristic electrocortical synchronization in the form of recruiting responses that mimic some sleep stages. It also inhibits input of irrelevant sensory stimuli, thus facilitating the process of selective attention. Permanent disruption of the system, via lesioning or temporary inactivation through cooling of the ITP with cryoprobes, results in a state of hyperkinesia, increased attention, and cortical desynchronization. RESULTS: Surgical lesioning of the medial part of orbitofrontal cortex and white matter overlying area 13, which includes the ITP, may result in significant improvement in MDD. Imaging studies (functional magnetic resonance imaging and positron emission tomography) consistently demonstrate hyperactivity in the orbitofrontal cortex and midline thalamic regions during episodes of MDD. This hyperactivity decreases with efficient control of MDD by medical treatment, indicating that orbitofrontal cortex and midline thalamic overactivity are related to the depressive condition. Conversely, noradrenergic and serotoninergic systems in the frontal lobes have been implicated in the pathophysiology of MDD. Although noradrenergic receptor density in the frontal lobe is consistently increased in depressed patients who commit suicide, 5-hydroxytryptamine reuptake blockers, which are potent antidepressive drugs, decrease hypermetabolism in the orbital frontal cortex in MDD. Therefore, the serotonin hypothesis for depression postulates that norepinephrine and serotonin in the frontal lobes are required to maintain antidepressive responsiveness. Dysregulation of the secretion of both neurotransmitters initiates overactivity of orbitofrontal cortex, resulting in depression. It is possible that surgical interventions in this region, including electrical stimulation of ITP, disrupt adrenergic and serotoninergic dysregulation in patients with MDD. CONCLUSION: Circumscribed lesions or electrical stimulation of the ITP, a discrete target easily identified by electrophysiological studies, may improve MDD. Electrical stimulation may have the advantage of being less invasive and more adjustable to patient needs.

Effect of Chronic Electrical Stimulation of the Centromedian Thalamic Nuclei on Various Intractable Seizure Patterns: II. Psychological Performance and Background EEG Activity

We studied the effect of electrical stimulation of centromedian thalamic nuclei (ESCM) on seizure control and paroxysmal EEG activity in 23 patients. We report the effect of chronic ESCM on psychological performance and background EEG activity of patients with various intractable seizure patterns. In each patient, a simple specifically designed neuropsychological scales (one for adults and one for children) was administered at the end of the baseline (BL), ESCM, and poststimulation (Post) periods; and 14 consecutive EEG recordings during these periods were performed to determine the degree of neuropsychological improvement and the temporal course of EEG changes. A significant increase in psychological scores and the number of background EEG waves per 10 s was noted in groups A (generalized tonic‐clonic seizures, GTC), C (complex partial seizures, CPS), and D (generalized tonic seizures) and the total group of patients from BL to ESCM and from BL to Post periods. Group B patients showed a substantial increase (partial motor seizures) during the same periods. Improvement on psychological performance correlated better with age and baseline degree of deterioration than with the nature of the particular psychological improvement in any given subtest. The improvement in EEG background rhythm was most noticeable at the end of ESCM and at the beginning of the Post periods. Complete normalization of neuropsychologic scores and EEG rhythms was rare, but improvement was significant for both. Psychological scores increased from BL 14 ± 2 to ESCM 21 ± 2 and Post 23 ± 2 (normal expected 26), and EEG background rhythm increased from BL 42 ± 2 to ESCM 62 ± 2 and Post 54 ± 2 EEG waves/10 s. (normal expected >80).

Subthalamic Prelemniscal Radiation Stimulation for the Treatment of Parkinson's Disease: Electrophysiological Characterization of the Area

Previous reports have provided evidence of a reticulo-thalamic system, extending from the mesencephalic reticular formation (MRF) to the ventrolateral thalamus (VL), involved in the production of tremor. In humans, a funnel of fibers in the posterior subthalamus named the prelemniscal radiations (Raprl) has been described as an exquisite target to treat tremor in cases of Parkinsons disease. In the present study, a group of 14 patients suffering from Parkinsons disease, with prominent unilateral tremor and rigidity, were implanted with tetrapolar depth brain stimulation (DBS) electrodes in Raprl to perform chronic electrical stimulation (ES) for the treatment of patient symptoms. Electrodes were left externalized to corroborate their placement throughout MRI studies and also to perform the following electrophysiological battery: (a) recording of somatosensory-evoked responses (SEP) through different electrode contacts and scalp by means of a paradigm to study the attention process; (b) evoking scalp EEG responses by stimulation with low (3 cps, 6 cps) and high (60-120 cps) frequencies with stimuli delivered through different electrode contacts, and (c) studying recovery cycle (RC) potentials in the Raprl while the upper MRF was being stimulated and, conversely, the RC in MRF while Raprl was being stimulated, before and after subacute Raprl stimulation. Thereafter, the electrodes were internalized and connected to a pulse generator (IPG) to carry on chronic ES, while the effects of stimulation were determined through a quantitative evaluation that measured phasic and tonic muscular activity with EMG recordings during different motor tasks. Results indicate the following: (a) that late, but not early, SEP components were recorded in Raprl and modulated in different attentive conditions; (b) that bilateral recruiting responses and spike and wave complexes were elicited by Raprl through low-frequency stimulation, while bilateral positive DC shifts induced by high-frequency stimulation were recorded, similar to those obtained in animals from MRF, and (c) that Raprl-ES induced RC inhibition at Raprl, but Raprl ES did not change MRF-RC. Long-term Raprl-ES induced a significant decrease in tremor and rigidity. It was concluded that Raprl represents a subthalamic circuit electrophysiologically related to MRF in the genesis of tremor and rigidity and in the process of selective attention. Raprl-ES induced a significant improvement in tremor and rigidity by causing inhibition of the stimulated area.