ABSTRACT
INTRODUCTION: Tribute to Robert Heath, M.D. a pioneer in human implanted corticosubcortical microelectrodes. OBJECTIVES: We evaluate retrospective electroencephalography (EEG), local evoked potentials (LEP) and extracellular unitary activity (EUA) of patients with diagnosis of panic disorder in association of simple partial seizures. These patients had presences or absence of agoraphobia. They received treatment with clonazepam or diazepam. PATIENTS AND METHODS: Ten patients with implanted corticosubcortical were divided in two groups. The five patients of group A were treated with clonazepam and the five patients of group B with diazepam. RESULTS: Panic attacks showed EEG thetha activity, increased amplitude of the negative phase of LEP, and an increase in the frequency of EUA in cortico-subcortical organizations. This changes occurred in all organizations with exception of the inhibitory reticular substance. Panic disorder produced abundance of repetitive epileptiform discharges that could precipitate convulsive crisis. Both benzodiazepines were efficacious although results with clonazepam were observed earlier: at 7 to 14 days. Benzodiazepines increased corticosubcortical EEG beta activity, decreased amplitude of negative phase of LEP, and diminution in the frequency of EUA. This changes occurred with exception on the inhibitory reticular system. We postulate: a) That panic disorder hyperexcitability at the cortico-subcortical neuronal level may be the result of gabergic dysfunction, or alteration in neuroinhibitory mechanism through GABAA receptors, and through GABAB neuromodulator receptors, and b) That there is a direct correlation between GABA inhibitory basic mechanism and electroencephalographic beta activity. CONCLUSIONS: Panic disorder produces neuronal hyperexcitability by gabergic dysfunction both benzodiazepines were efficacious in treatment.
Subject(s)
Anti-Anxiety Agents/pharmacology , Cerebral Cortex/drug effects , Clonazepam/pharmacology , Diazepam/pharmacology , Electroencephalography/drug effects , Panic Disorder/drug therapy , Adult , Anti-Anxiety Agents/therapeutic use , Cerebral Cortex/physiopathology , Clonazepam/therapeutic use , Diazepam/therapeutic use , Electrodes, Implanted , Electroencephalography/instrumentation , Evoked Potentials/drug effects , Female , Humans , Male , Microelectrodes , Nerve Tissue Proteins/drug effects , Nerve Tissue Proteins/physiology , Neurons/drug effects , Neurons/physiology , Panic Disorder/physiopathology , Receptors, GABA-A/drug effects , Receptors, GABA-A/physiology , Retrospective Studies , gamma-Aminobutyric Acid/physiologyABSTRACT
Introducción. Robert Health fue pionero en implantar microelectrodos córtico-subcorticales en el humano. Objetivos. Evaluar los resultados retrospectivos EEG, potenciales evocados locales (PEL) y actividad unitaria extracelular (AUE) de pacientes con trastornos de pánico (TP) asociado con crisis parciales simples del lóbulo temporal, con o sin agorofobia, que fueron tratados con clonacepam y diacepam. Pacientes y métodos. Se implantaron microelectrodos subcorticales a 10 pacientes, divididos en dos grupos de cinco, A y B. Analizamos los efectos de clonacepam en el grupo A y los de diacepam en el grupo B. Resultados. El ataque de pánico produce abundante actividad theta en el EEG, incremento de amplitud fase negativa de PEL y aumento en frecuencia de AUE en organizaciones córtico-subcorticales, a excepción del efecto opuesto en la sustancia reticular inhibitoria. Además, incrementa las descargas epileptiformes que pueden conllevar crisis convulsivas. Las benzodiacepinas son eficaces en la clínica. El EEG muestra incremento de la actividad beta, PEL disminución de la fase negativa y disminución de la frecuencia de AUE y de las descargas epileptiformes. En el ámbito de la sustancia reticular inhibitoria los efectos son opuestos. Postulamos hiperexcitabilidad neuronal córticosubcortical y ocasionalmente crisis convulsivas durante TP secundaria a disfunción gabérgica, que altera los mecanismos neuroinhibitorios a través de receptores de GABA A y neuromoduladores a través de GABA B. Las benzodiacepinas muestran husos benzodiacepínicos en el EEG e incremento inhibitorio en PEL y AUE córtico-subcortical a excepción del efecto opuesto en la sustancia reticular inhibitoria, que se manifestó por desinhibición de la inhibición y que fue establecida durante TP por el sistema reticular excitatorio bajo la acción del mecanismo de filtro. Conclusión. Los TP hiperexcitabilidad neuronal por disfunción gabérgica. Eficacia de benzodiacepinas mayor para clonacepam (AU)
Subject(s)
Adult , Male , Female , Humans , Anti-Anxiety Agents , Panic Disorder , Microelectrodes , Neurons , Nerve Tissue Proteins , Receptors, GABA-A , Retrospective Studies , Cerebral Cortex , Clonazepam , Diazepam , Electroencephalography , Electrodes, Implanted , Evoked Potentials , gamma-Aminobutyric AcidABSTRACT
INTRODUCTION: Trigeminal neuralgia is an unilateral alteration of the trigeminal nerve, characterized by recurrent paroxysms of pain in one or more of the nerve's branches. Trigger areas are described in points of the facial skin (allodynia). OBJECTIVE: To evaluate the effects of gabapentin (monotherapy) and associated with carbamazepine in allodynia of trigeminal neuralgia. PATIENTS AND METHODS: The effects of these drugs were studied in 14 patients with trigeminal allodynia and with 12 experimental cats, with microelectrodes of multiple connections in the central nervous system and in dental pulp to precipitate pain in injured zones, area of primary hyperalgesia, secondary hyperalgesia and allodynia zone. Unitary registrations and evoked potentials were evaluated in neuronal trigeminal organizations, encephalon, limic system and neocortex. RESULTS: The pairing of innocuous stimulus (allodynia) plus painful stimulus precipitate classic conditioned reflex. Unitary alteration and evoked potentials correlated with learning and memory were evaluated, involving the hippocampus in the results. The allodynia treatment obtains better results with the combined treatment than with the monotherapy. CONCLUSIONS: Allodynia can be the result of a neuronal sensitization due to the increment on intracellular calcium facilitating the exocytosis. Changes in the mechano-receptors of low threshold establish communication with nociceptive neurons by a presynaptic mechanism, considering new synaptic and morphologic contacts associated with learning and memory. The major effectiveness in the combined treatment is the base of an association of the gabaergic mechanism of gabapentin and the blockade of sodium and potassium ionic channels by the carbamazepine.
Subject(s)
Acetates/therapeutic use , Amines , Cheek/innervation , Cyclohexanecarboxylic Acids , Facial Muscles/innervation , Trigeminal Neuralgia/drug therapy , gamma-Aminobutyric Acid , Adult , Aged , Analgesics, Non-Narcotic/therapeutic use , Animals , Calcium/metabolism , Carbamazepine/therapeutic use , Cats , Cell Communication/physiology , Conditioning, Classical/physiology , Electrodes, Implanted , Evoked Potentials/physiology , Female , Gabapentin , Hippocampus/physiology , Humans , Intracellular Membranes/metabolism , Male , Medicine in the Arts , Middle Aged , Neurons/metabolism , Nociceptors/metabolism , Paintings , Trigeminal Neuralgia/etiologyABSTRACT
Findings in this study support earlier investigations in attesting to the antipsychotic efficacy and relatively low toxicity of pipotiazine palmitate. Results with all efficacy measures utilized were consistent in indicating a high level of efficacy for this investigational compound. Pipotiazine palmitate apparently has an average duration of action that extends beyond 4 weeks in severely ill schizophrenic patients. This particular long acting IM antipsychotic preparation appears to have an even longer duration of activity than some of the other available standard long acting agents. The optimal dosage range for severely ill schizophrenic patients appears to be between 100 and 600 mg once monthly. While this type of drug (as is the case with many antipsychotic drugs) does reduce the psychotic symptomatology and improves the thought associations sufficient to enable the patient to leave the hospital, it should be re-emphasized that socioeconomic and guidance counseling services are necessary to maintain the patient in the community. The availability of this type of long acting preparation is not only economical in terms of nursing care and hospital cost but it should also increase the efficacy of psychopharmacologic treatment of schizophrenics by reducing both patient errors and staff errors in administration of medication. In addition, this IM preparation should prove to be of invaluable help in maintaining the schizophrenic patient in his community by reducing the relapse and the rehospitalization rates. It should be noted that there are schizophrenic patients who either absorb compounds from the gastrointestinal tract in a very poor manner or too rapidly metabolize the antipsychotic agents with resultant suboptimal blood levels and these subjects may be called "drug refractory." This type of long acting medication is an ideal preparation for the schizophrenic patient who has these types of absorption or metabolic problems since the "circulatory pass" through the liver is minimal after IM medication as compared to that encountered by an orally administered agent. The clinical disadvantage of pipotiazine palmitate is the delay in onset of therapeutic activity after injection. Significant improvement is first noted after 3 to 4 days after the highest IM dosage administration. Therefore, it may be necessary to use an oral or IM preparation of a neuroleptic with a more rapid onset of activity or utilize an oral dosage of the pipotiazine salt during the first week following IM administration of pipotiazine palmitate.
