Computer analysis of EEG activity in dementia of the Alzheimer's type and Huntington's disease.

Computer analysis of the EEG was obtained in the course of evaluation of 35 patients with Dementia of the Alzheimer's Type (DAT) and Huntington's disease (HD), and compared to 20 age-matched normal controls. On-line computer analysis of the EEG consisted of: 1) compressed spectral array (CSA) displays (2-6 channels); 2) relative frequency power (4 bands) and 3) an averaged frequency power function [( alpha/alpha + theta power (microV 2)] X 100 = % EEG Power function). Frequency power reflected increased theta, and reduced alpha components, in patient groups. Significant correlation was obtained between % EEG Power function, and clinical stage of dementia. This function correctly identified 17/25 DAT, and 7/10 HD patients, and gave additional quantification to the primary EEG.

Hyperekplexia exacerbated by occlusion of posterior thalamic arteries.

A 65-year-old man with the onset of hyperekplexia at 37 years of age experienced resolution of the illness at the age of 45 years. Twenty years later after a posterior thalamoperforate artery occlusion that produced a "rubral tremor," severe hyperekplexia redeveloped. The patient's symptoms were controlled with clonazepam, except for brief periods. Interruption of the rubrothalamic pathways or neuronal aggregates at the level of the red nucleus seemed to disinhibit the startle reflex.

Generalized cortical electrodecremental event. Clinical and neurophysiological observations in patients with dystonic seizures.

Patients with seizures accompanied by generalized cortical electrodecremental event (CEE) have clusters of clinical spells with tonic, dystonic, or atonic components and involvement of autonomic functions. When electroencephalographically detectable foci are present, they behave in a peculiar way; throughout the entire cluster of seizures focal spiking is reduced in the short interictal periods as well as during each individual seizure with CEE, at which time it is suppressed. Focal firing reappears reinforced at the end of each spell and also at the end of the cluster. These facts suggest that the foci responsible for CEE are deeply located. A complex excitatory-inhibitory feedback probably exists between cortical and subcortical foci. These seizures should be differentiated from similar attacks of nonepileptic or epileptic nature. A correct diagnosis is essential given the different therapeutic implications.

EEG in phenylketonuria. Attempt to establish clinical importance of EEG changes.

To determine the importance of an abnormal EEG in phenylketonuria (PKU), we reviewed 137 EEGs from 48 patients with PKU. Patients were divided into three groups: group 1 (n = 14) had only normal EEGs, group 2 (n = 20) had only abnormal EEGs, and group 3 (n = 14) initially had normal EEGs that later became abnormal. The most common EEG abnormality was focal paroxysmal discharge. Patients in group 2 started treatment at a later age an had a greater frequency of seizures and mental retardation. Phenylalanine levels greater than 20 mg/dL were more often associated with abnormal EEGs. Older patients were more likely to have abnormal EEGs; 78% of the 41 patients who had EEGs at age 6 or older had abnormal records, whereas only 15% of the 26 patients who had EEGs before the age of 6 had abnormal records. Conventionally treated patients with classic PKU and normal EEGs in infancy may have abnormal EEGs when retested later even though they remain on a restricted diet. Although not usually associated with clinical deterioration, abnormal EEGs may unveil the presence of CNS dysfunction even when a child is in satisfactory clinical condition.

The prepiriform cortex in dementia of the Alzheimer type.

Histopathologic examination of the prepiriform cortex (PPC) in four documented cases of dementia of the Alzheimer type revealed increased numbers of neurofibrillary tangles and neuritic plaques. These findings indicate that some early- and late-onset cases of Alzheimer's disease may be associated with significant damage to the PPC, a relay center of the mammalian olfactory system that has extensive connections with structures concerned with cognitive and behavioral functions. Involvement of the PPC may be related to the complex neuropsychiatric manifestations observed in this disorder.

Familial and acquired paroxysmal dyskinesias. A proposed classification with delineation of clinical features.

On a clinical basis the paroxysmal dyskinesias can be classified into two distinct categories--familial and acquired. The former begins in childhood and the dyskinesia may or may not be induced by sudden movements (kinesigenic or nonkinesigenic forms). In the familial kinesigenic form, the movements are brief, usually occur daily, and respond readily to anticonvulsants. This form has an autosomal dominant or recessive mode of inheritance. In the familial nonkinesigenic form, the movements are of longer duration, occur less frequently, and rarely respond to anticonvulsants. This form has a clear autosomal dominant mode of inheritance. The etiology is obscure. The acquired form of paroxysmal dyskinesia has a later onset and is an expression of an underlying neurological or metabolic disease. Some cases of acquired paroxysmal dyskinesia are manifestations of unusual forms of epilepsy. In these cases the differential diagnosis may be extremely difficult and must be based on EEG findings during an ictal episode.

EEG recognition of Aicardi's syndrome.

Thirty-two EEGs from six cases of Aicardi's syndrome were reviewed. A characteristic EEG pattern was found in all cases. This consists of multifocal epileptiform abnormalities occurring on a burst-suppression pattern showing complete asynchrony between the two hemispheres. This pattern has been described so far only in Aicardi's syndrome. These characteristic EEG features are more readily found early in the course of the disease and occur less frequently six months after from the onset of symptoms, at which time they are often replaced by multiple epileptic foci on a severely disorganized background. The EEG sleep pattern was profoundly altered in all stages of the disease. The EEG is considered a helpful tool in the diagnosis of Aicardi's syndrome.

Cortical and subcortical projected foci in cats: inhibitory action of taurine.

The effects of local application of taurine and isethionic acid on the propagation of the epileptic activity to the mirror area in cats have been studied. Cortical and amygdaloid acute foci were induced by local administration of conjugated estrogens. Taurine proved to be effective in reducing and sometimes in abolishing the appearance of the epileptic propagated elements in the mirror area. When this agent was applied 30 minutes before the induction of the primary focus, the single spike transmission was reduced or prevented; however, the transmission of a seizure was not blocked. No changes in the transmitted phenomena were observed when isethionic acid was administered with the same technique as that used for taurine. The present study stresses the clear antiepileptic activity of taurine in this experimental model, ruling out the possibility of an unspecific interaction with the epileptogenic agents. Moreover, it is suggested that the deamination of taurine is not important for its antiepileptic action.

Homotaurine (3 aminopropanesulfonic acid; 3APS) protects from the convulsant and cytotoxic effect of systemically administered kainic acid.

Pretreatment of rats with homotaurine (3 aminopropanesulfonic acid; 3APS), a synthetic gamma-aminobutyric acid (GABA) analog, protected from the convulsant and cytotoxic action of systemically injected kainic acid (KA). Wet dog shaking (WDS) behavior was significantly reduced. Taurine, an inhibitory non-GABA-mimetic amino acid, and muscimol (another direct GABA-agonist) reduced the number of seizures and lesions in the brain but were less effective than homotaurine. Progabide (a GABA-agonist) did not modify kainic acid effects. The neurotoxicity of kainic acid could have been due to repetitive convulsive activity. Activation of GABA-mediated inhibition is an effective, but not the determinant means of preventing KA-induced abnormalities.

Ketamine activation of experimental corticoreticular epilepsy.

Generalized corticoreticular epilepsy was established in adult cats by parenteral penicillin, and electroencephalographic monitoring was carried out. Ketamine HCl was injected intravenously in doses of 2.5 to 20 mg per kilogram. If doses of penicillin were inadequate to establish typical spike-wave activity, ketamine induced the spike-wave pattern typical of much higher doses of penicillin. At doses of penicillin that established the spike-wave pattern, ketamine potentiated the spike-wave activity and sometimes induced spike-and-wave status. These findings suggest caution in the clinical use of ketamine in patients with corticoreticular epilepsy. Because analogous effects have been observed upon administration of GABA-mimetic agents, GABA systems may play a role in ketamine anesthesia and corticoreticular epilepsy. Precollicular brain transections failed to modify ketamine effects, excluding a possible influence of mesencephalic centers on the observed potentiation.

Reenactment of the triggering situation for the diagnosis of epilepsy.

When a fixed set of ambient circumstances is associated with convulsive or nonconvulsive paroxysmal attacks, reenactment of the situation should be considered as a possible shortcut for reaching a diagnosis. Reenactment determined the diagnosis in 30 of 32 patients with paroxysmal disorders. The referral diagnosis was correct in only 13 of the 32 patients. To be appropriately executed, the reenactment should entail polygraphic recording of at least EEG, ECG, and respiration. Vertex electrodes should be included to avoid overlooking of cortical electrodecremental event. If unsuccessful at the first attempt, reenactment should be repeated.

Epileptogenic action of intraventricularly injected antimelatonin antibody.

In rats, intraventricularly injected antimelatonin antibody caused the appearance of transitory epileptiform abnormalities. Epileptic activity arose from and was limited to the cortical mantle of the hemisphere ipsilateral to the injection side. The occasional occurrence of lateralized seizures has also been observed. Control injection of saline, of the vehicle (rabbit serum), or of antibody saturated with melatonin induced flattening and desynchronization of the electroencephalogram but not epileptiform activity. Repeated antimelatonin injections caused reappearance of the same type of epileptic abnormalities that lasted slightly longer than the first time. Melatonin may play an inhibitory role in neuronal excitability.

Anti-allodynic effect of NW-1029, a novel Na(+) channel blocker, in experimental animal models of inflammatory and neuropathic pain.

NW-1029, a benzylamino propanamide derivative, was selected among several molecules of this chemical class on the basis of its affinity for the [(3)H]batracotoxin ligand displacement of the Na(+) channel complex and also on the basis of its voltage and use-dependent inhibitory action on the Na(+) currents of the rat DRG (dorsal root ganglia) sensory neuron. This study evaluated the analgesic activity of NW-1029 in animal models of inflammatory and neuropathic pain (formalin test in mice, complete Freund's adjuvant and chronic constriction injury in rats) as well as in acute pain test (hot-plate and tail-flick in rats). Orally administered NW-1029 dose-dependently reduced cumulative licking time in the early and late phase of the formalin test (ED(50)=10.1 mg/kg in the late phase). In the CFA model, NW-1029 reversed mechanical allodynia (von Frey test) after both i.p. and p.o. administration (ED(50)=0.57 and 0.53 mg/kg), respectively. Similarly, NW-1029 reversed mechanical allodynia in the CCI model after both i.p. and p.o. administration yielding an ED(50) of 0.89 and 0.67 mg/kg, respectively. No effects were observed in the hot-plate and tail-flick tests up to 30 mg/kg p.o. The compound orally administered (0.1-10 mg/kg) was well tolerated, without signs of neurological impairment up to high doses (ED(50)=470 and 245 mg/kg in rat and mice Rotarod test, respectively). These results indicate that NW-1029 has anti-nociceptive properties in models of inflammatory and neuropathic pain.

The THIP-induced model of bilateral synchronous spike and wave in rodents.

Intraperitoneal administration of 5-10 mg/kg of THIP (4,5,6,7 tetrahydroxyisoxazolo (4,5,c) pyridine 3-ol) induced a transient, reliable model of bilaterally synchronous spikes and waves in rats. The paroxysmal bursts elicited by THIP had similar topographical distribution to the spontaneously-occurring spike and wave discharges often observed in naive rats. The responsiveness to electrical stimulation of subcortical nuclei was different in the two models. Systemic administration of THIP provided a simple, reliable model of bilaterally synchronous spike and wave discharges that may involve the same cerebral structures as those involved in the generation of the spontaneous paroxysms. The administration of the drug increased the yield of paroxysmal responses and provided a stable and predictable 4 hr test situation that may easily be quantified.

Evidence for an epileptogenic action of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine.

Based on behavioral observation alone, poorly characterized paroxysmal motor abnormalities have been reported in mice after acute MPTP administration. This study investigated electroencephalographic (EEG) and behavioral effects of acute MPTP in young and older mice. Single MPTP injections (30 mg/kg i.p.) produced limbic and/or generalized seizures in older (6 mo) and frank epileptiform interictal hippocampal spikes in younger (6-8 wks) mice. These latter showed behavioral seizures only after the 3rd drug administration. Studies of the acute effects of MPTP must take in consideration that seizures "per se" modify brain biochemical and metabolic activity and alter the permeability of the blood brain barrier, adding several confounding variables.

Penicillin spikes in rats. Limitations of a simple model for the study of anticonvulsants.

Direct GABA agonists that suppress spikes induced by penicillin in cats failed to do so in rats. Phenytoin and large doses of THIP increased the rate of spiking activity of the penicillin focus. Only progabide caused marked, initial, short-lasting suppression and a modest reduction of frequency of spikes for 1 hr. Homotaurine (3APS) reduced the amplitude and changed the morphology of the contralateral "mirror" spike. Antagonism of penicillin-induced spikes in rats is considered to be an unsuitable parameter for the screening of anticonvulsant agents.

Transient nigral ubiquinone depletion after single MPTP administration in mice.

The administration of a single injection of 30 mg/kg MPTP to mice produces at 1 hr, a transient significant decrease of the reduced ubiquinol Q10 in the substantia nigra that is normalized afterwards. This suggests a transient stress imposed by MPTP (or more likely MPP+) in the mitochondrial respiratory and/or oxidoreducing system, located in close proximity to the NADH system.

Regional distribution of ubiquinones and tocopherols in the mouse brain: lowest content of ubiquinols in the substantia nigra.

C57 black mice of 3 months of age were sacrificed, and their brain regionally dissected according to a protocol that strickly control for the death-freezing interval of each region. HPLC measurements of tocopherols and oxidized and reduced ubiquinones demonstrated significant regional variations. The substantia nigra had the lowest content of Q10 and a skewed ratio in favor of its oxidized form. Forebrain cholinergic nuclei had also more oxydized than reduced Q10 and in addition the lowest content of tocopherols. These findings suggest that nuclei that show neuronal depletion with age are the ones prone to oxidative stress.

Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on levels of glutathione in the extrapyramidal system of the mouse.

Treatment of mice with the proximate neurotoxin MPTP depletes striatal dopamine levels. Depletion of striatal dopamine and metabolites in MPTP-treated mice is accompanied by depletion of glutathione (GSH) in the substantia nigra (SN). Striatal GSH and nigral amino acid levels were not significantly affected by MPTP. Results suggest that GSH depletion in SN may represent an index of regional vulnerability to metabolic oxidative stress and also of selective susceptibility to the toxic effects of MPTP.

Transient seizure activity induced by acetylcarnitine.

Intracerebral injection of L-acetylcarnitine in rats induced interictal and ictal epileptic phenomena with immediate onset, lasting up to 4 h. Pretreatment with systemic atropine prevents all epileptiform phenomena. Local injection of muscimol and THIP abolish ictal events, but not single spikes. L-carnitine induced only ictal discharges with a latency of 40-90 min. Acetylcarnitine epileptogenic properties are probably related to muscarinic agonism. The transition from interictal to ictal events may involve failure of GABAergic mechanisms.