Transient unresponsiveness in the elderly: possible episodes of idiopathic recurring stupor.
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Aged↗
Biomedical subjects
P Tinuper
Publications and source records attributed to P Tinuper.
Sleep-wake cycle abnormalities in fatal familial insomnia. Evidence of the role of the thalamus in sleep regulation.
Alterations in sleep organization were longitudinally studied in 6 new cases of fatal familial insomnia (FFI) by 24 h polygraphic recording. All patients showed an early reduction in sleep spindles and K complexes, and a drastic reduction in total sleep time and disruption of the cyclic sleep organization. Complete abolition of NREM sleep and persistence of only brief residual periods of REM sleep without atonia were features characteristic of the 3 patients with a short (less than 1 year) clinical course, and lacking in the 3 cases with a longer (more than 2 years) disease course. In the latter, sudden transitions from waking to NREM or REM sleep occurred, sometimes recurring periodically. Our findings confirm that impairment of sleep-wake regulation is a consistent distinctive feature of FFI.
Adult↗
Plasma endogenous benzodiazepine-like activity in sleep disorders with excessive daytime sleepiness.
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Adult↗
Idiopathic recurring stupor.
Idiopathic recurring stupor (IRS) is a disease of unknown pathogenesis presenting with recurrent stuporous states. We describe three IRS patients in whom there were no metabolic, toxic, or structural brain dysfunctions. Ictal EEGs were characterized by fast (14- to 16-Hz), unreactive background activity. Flumazenil, a benzodiazepine receptor antagonist, promptly resolved the clinical and EEG picture. In all patients, ictal plasma determination showed a marked increase in benzodiazepine-like activity identified as endozepine-4. IRS may be due to an unexplained excess of endozepine-4.
Adult↗
Paroxysmal periodic motor attacks during sleep: clinical and polygraphic features.
Three patients complained of paroxysmal motor attacks during sleep. Videopolygraphic recordings showed that motor activity could be divided into events of increasing behavioural complexity. Simpler motor events often represented the initial fragment of more complex attacks. Clinical features suggested the attacks represented frontal lobe epileptic seizures. The attacks recurred during NREM sleep with a periodic repetition every 20-60 sec. This periodicity could be related to the analogous physiological oscillation during light sleep and the periodicity of K complexes, exerting a facilitating influence upon epileptic mechanisms.
Adult↗
[18F]FDG PET in fatal familial insomnia: the functional effects of thalamic lesions.
We used [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) to study regional cerebral glucose utilization (rCMRglc) in four patients with fatal familial insomnia (FFI), a prion disease with a mutation at codon 178 of the prion protein gene. Two patients, presenting only with insomnia and dysautonomia, had a prominent and, in one case, selective thalamic hypometabolism. The remaining two cases presented a more complex clinical picture with multiple neurologic deficits, with both thalamic and widespread brain hypometabolism involving the majority of cortical structures, basal ganglia, and the cerebellum. This widespread pattern was present in the early stage of the disease and showed significant worsening as the disease progressed in one patient examined twice. The thalamic hypometabolism, consistently found with PET in FFI patients, is in agreement with the neuropathologic findings and is a hallmark of the disease.
Adult↗
Endogenous benzodiazepine receptor ligands in idiopathic recurring stupor.
"Endozepines" are endogenous ligands for the benzodiazepine recognition sites on gamma-aminobutyric acid A receptors in the nervous system. Idiopathic recurring stupor (IRS) is a syndrome of spontaneous stupor or coma that is not associated with known metabolic, toxic, or structural abnormalities but can be reversed by flumazenil, a pure benzodiazepine antagonist. We measured endozepine-2 and endozepine-4 by high-performance liquid chromatography and radioreceptor assay in serum and cerebrospinal fluid from three patients with IRS. During episodes of stupor there was a large (up to 300-fold compared with control patients) increase of endozepine-4 content in cerebrospinal fluid and serum, but a return to normal concentrations between attacks. Endozepine-4 may contribute to, or be the cause of, IRS. The reasons for abnormal concentrations of endozepine in blood and brain are unknown.
Adult↗
Idiopathic recurring stupor: a case with possible involvement of the gamma-aminobutyric acid (GABA)ergic system.
A patient had recurrent spontaneous episodes of stupor or coma in the absence of toxic, metabolic, or structural brain damage. Ictal electroencephalography showed fast 14 Hz background activity; sleep studies excluded narcolepsy. Flumazenil (Anexate), a benzodiazepine antagonist, promptly resolved the episodes and normalized the electroencephalogram. Radioreceptor binding studies showed the presence of a ligand to the central benzodiazepine receptor in plasma and cerebrospinal fluid during the episodes, suggesting a gamma-aminobutyric acid (GABA)ergic system involvement in the origin of the attacks.
Benzodiazepines↗
Abnormal sympathetic skin responses in thalamic lesions.
Sympathetic skin responses (SSRs) were abolished in 4 patients affected with fatal familial thalamic degeneration involving the anterior (A) and dorsomedial (DM) thalamic nuclei, without lesions of the peripheral vegetative system. Abnormalities of SSR were not due to peripheral nerve lesions. It is concluded that SSR integrity also depends upon thalamic formations ("visceral" thalamus) and their frontal cortical connections.
Adult↗
Brain energy metabolism studied by 31P-MR spectroscopy in a case of migraine with prolonged aura.
The brain and skeletal muscle oxidative metabolism of a patient with prolonged aura was studied by phosphorus magnetic resonance spectroscopy. We found that the phosphocreatine to ATP ratio in brain was reduced, while the inorganic phosphate to phosphocreatine ratio and the calculated ADP concentration were increased. The phosphorylation potential and percentage of maximal rate of ATP synthesis were also altered. Intracellular pH and inorganic phosphate concentration were normal. In muscle we found a low post-exercise recovery of phosphocreatine. These data indicate an impairment of energy oxidative metabolism both in brain and muscle.
Adenosine Diphosphate↗
Fatal familial insomnia: clinical and pathologic study of five new cases.
In 1986, we reported two anatomoclinical observations of a familial condition that we called "fatal familial insomnia" (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with "torpedoes," and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined.
Adult↗
Fatal familial insomnia: a second kindred with mutation of prion protein gene at codon 178.
Fatal familial insomnia (FFI), a condition characterized by inability to sleep, dysautonomia, motor disturbances, and selective thalamic atrophy is a prion disease linked to a GAC----AAC mutation at codon 178 of the prion gene. These data were obtained from one kindred. We now report a second kindred affected by FFI and carrying the same mutation. The finding of the same disease phenotype and genotype in a second family further validates FFI as a distinct disease entity and a phenotype of the GAC----AAC mutation at codon 178 of the prion gene.
Base Sequence↗
Cardiovascular dysautonomia in fatal familial insomnia.
Autonomic control of the cardiovascular system was assessed in two patients with Fatal Familial Insomnia. The diagnosis was confirmed at autopsy in patient 1. In the resting state blood pressure and heart rate were higher than controls in patient 1; plasma noradrenaline levels were elevated in both patients. Evaluation of cardiovascular reflexes indicated intact baroreflex pathways but with exaggerated blood pressure and biochemical responses to certain stimuli (postural change, Valsalva manoeuvre, isometric handgrip). There was no pressor response to intravenously infused noradrenaline, an increased response to atropine and diminished depressor and sedative effects to clonidine. Overall these results are indicative of an unbalanced autonomic control with preserved parasympathetic and higher background and stimulated sympathetic activity. These physiological, biochemical and pharmacological data, together with known neuro-pathological findings in this disorder, emphasize the possible role played by the thalamus in regulating autonomic control of cardiovascular function in man.
Adult↗
Migraine with aura and photosensitive epileptic seizures: a case report.
An 18-year-old female presented with two seizures induced by photic stimulation. She had a positive family history for migraine and a history of febrile convulsions. Since the age of 13 she had suffered from migraine attacks with aura. A brain computerized tomography with contrast enhancement was negative and several electroencephalograms showed a photoparoxysmal response. At the age of 18 she had a partial secondary generalized seizure after photic stimulation during routine electroencephalogram. The onset of seizure was in the occipital region. Two days later, the patient presented with a typical migrainous attack with aura. Interictal apomorphine test (1.5 mg s.c.) blocked the photoparoxysmal response. According to Quesnay, dopaminergic failure of the occipital cortex may account for both epileptic and migraine features.
Adolescent↗
Circadian hormonal rhythms in two new cases of fatal familial insomnia.
We used a chronobiological inferential statistical method to investigate circadian rhythms of hypophyseal hormones, cortisol, melatonin and catecholamines in two females of the same family affected by fatal familial insomnia. Case 1 (confirmed at autopsy) presented an absent or progressive loss of circadian rhythms of all hormones. In case 2 there was a loss of GH circadian rhythm and a less significant rhythm for melatonin, catecholamines and gonadotropins. These results confirm the role of the thalamus in regulating hormonal circadian rhythm.
Adult↗
Electroencephalogram and HIV infection: a prospective study in 100 patients.
In order to study the correlation between central nervous system (CNS) involvement and EEG abnormalities in HIV infection we studied 100 consecutive HIV patients. Patients were divided into 4 groups; Group I: 42 neurologically asymptomatic subjects; Group II: 6 patients with peripheral neuropathies; Group III: 28 patients with AIDS Dementia Complex; Group IV: 24 patients with secondary CNS involvement. The results of this study emphasize that abnormal EEGs are correlated with CNS involvement. Neurologically asymptomatic patients showed no abnormal tracings, but the presence of borderline EEGs (33%) in asymptomatic patients should be evaluated prospectively.
AIDS Dementia Complex↗
Paroxysmal arousals during sleep.
Six patients complained of distressing sudden awakenings with abnormal motor activity during sleep causing insomnia. Polysomnography showed paroxysmal short-lasting arousals during NREM, especially slow-wave sleep, associated with complex movements and autonomic activation. Ictal and interictal EEG never showed epileptic discharges except in 1 patient who also had a tonic-clonic seizure during sleep. Carbamazepine was the only effective medication in 2 patients. Paroxysmal arousals represent a sleep disturbance that may be related to deep epileptic foci.
Adult↗