Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report here the first sleep deprivation study done on a group of 5 healthy students (1 female, 4 males, 23-24 years of age) while playing a game (Triviant). In 2 persons an EEG was recorded for 6 consecutive 24 h periods with an ambulatory monitor from the baseline night until 72 h after deprivation. The baseline night showed normal hypnograms. The students were deprived of sleep for 65 h following the baseline night. Sleep deprivation was complete and resulted in bradyphrenia, loss of memory and contact with reality, ataxia, decrease in body temperature and loss of body weight. The main sign of recuperation was a strongly increased slow-wave sleep synchronization during the first recuperation period (day-time sleep) only. There were no signs of REM rebound.
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PMID:Long-term sleep deprivation as a game. The wear and tear of wakefulness. 132 May 35

This is the first report of unilateral palatal myoclonus with which two different ocular movements were synchronized. A 55-year-old woman was admitted to our hospital due to intubation and dysarthria of sudden onset after three similar attacks for these four years. On admission right ptosis, hypalgesia in the right face, right facial nerve palsy, dysarthria, bilaterally increased deep tendon reflexes and trunkal ataxia were noted. Continuous repetitive contractions at 110/min frequencies were observed in the left soft palate, pharynx and larynx. On electronystagmography and electro-magnetic search coil system (Skala system), two different ocular movements, i.e., rotary oscillation with torsion and nystagmus to the right, successively alternated each other at random during eyelids closure. They were synchronized with palatal myoclonus. True nystagmus synchronized with palatal myoclonus has not been reported. When she calculated, rotary oscillation disappeared. In sleep polygraphy, rotary oscillation reduced in amplitude in stage 1 and disappeared in stages 2, 3, 4 and REM. On the other hand, the nystagmus reduced in amplitude in stage 1 and 2 and disappeared in stages 3, 4 and REM. The direction of nystagmus was converted to the left in stages 1 and 2. Similarly, in a drowsy state induced by intravenous injection of 7 mg diazepam, the direction of the nystagmus was converted to the left. On brain magnetic resonance imaging (MRI) right inferior olive was identified as a well circumscribed, enlarged increased signal area on T2-weighted and proton density-weighted images in addition to the lesions of infarcts in left corona radiata, posterior limb of right internal capsule and tegmentum pontis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Unilateral palatal myoclonus with peculiar ocular movements--neurotological studies and MRI]. 275 41

A clinical and polygraphic sleep study was carried out in nine patients affected by heredoataxia (three by sporadic olivopontocerebellar ataxia (SOPCA), three by early onset cerebellar ataxia (EOCA) and three by Friedreich's ataxia). None of the patients complained about subjective sleep complaints. Polysomnographic findings showed a decrease in REM time in all the patients considered and a lower REM density in SOPCA and EOCA. A pattern of obstructive sleep-apnea was found in one case of SOPCA.
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PMID:Polygraphic sleep patterns in heredoataxia: a study of nine cases. 376 34

To test the hypothesis that sleep produced by thalidomide, unlike that of pentobarbital, is associated with increased neuronal activity in the preoptic area (POA), the spontaneous activity of 96 POA neurons was recorded in chronically prepared cats during alert wakefulness (W), deep slow-wave sleep (SWS), and REM sleep in a drug-free preparation and after administration of thalidomide (4 mg/kg) and pentobarbital (4 or 8 mg/kg). Thalidomide, unlike pentobarbital, at a dose that significantly increased the amount of SWS, failed to depress neuronal activity in the POA compared to drug-free controls. Mean discharge rates during thalidomide treatment were similar to drug-free rates. In contrast, rates during low-dose pentobarbital treatment were significantly less than those of drug-free and thalidomide-treated animals. Rates during high-dose pentobarbital treatment were significantly less than those in all other groups. Thalidomide, compared with the other groups, in addition to increasing the amount of SWS, significantly increased the total amount of REM sleep as well as REM sleep as a percent of total sleep, but did not produce ataxia or behavioral excitement. These results do not confirm the initial hypothesis, but suggest that hypnotic drugs that do not depress neuronal activity in the POA may be devoid of some of the unwanted side effects often associated with the more commonly prescribed hypnotic medications.
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PMID:Effects of thalidomide and pentobarbital on neuronal activity in the preoptic area during sleep and wakefulness in the cat. 392 Jun 98

In 1989, we described a new autosomic-recessive myelin-mutant rat that develops a progressive motor syndrome characterized by tremor, ataxia, immobility episodes (IEs), epilepsy, and paralysis. taiep is the acronym of these symptoms. The rat developed a hypomyelination, followed by demyelination. At an age of 7-8 months, taiep rats developed IEs, characterized electroencephalographically by REM sleep-like cortical activity. In our study, we analyzed the ontogeny of gripping-induced IEs between 5 and 18 months, their dependence to light-dark changes, sexual dimorphism, and susceptibility to mild stress. Our results showed that IEs start at an age of 6.5 months, with a peak frequency between 8.5 and 9.5 months. IEs have two peaks, one in the morning (0800-1000 h) and a second peak in the middle of the night (2300-0100 h). Spontaneous IEs showed an even distribution with a mean of 3 IEs every 2 h. IEs are sexually dimorphic being more common in male rats. The IEs can be induced by gripping the rat by the tail or the thorax, but most of the IEs were produced by gripping the tail. Mild stress produced by i.p. injection of physiological saline significantly decreased IEs. These results suggested that IEs are dependent on several biological variables, which are caused by hypomyelination, followed by demyelization, which causes alterations in the brainstem and hypothalamic mechanisms responsible for the sleep-wake cycle regulation, producing emergence of REM sleep-like behavior during awake periods.
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PMID:Characterization of the spontaneous and gripping-induced immobility episodes on taiep rats. 1608 50

Bipedal locomotion and fine motility of hand and larynx of humans introduced musculoskeletal adaptations, new pyramidal, corticostriatal, corticobulbar, nigrostriatal, and cerebellar pathways and expansions of prefrontal, cingular, parieto-temporal and occipital cortices with derived new brain capabilities. All selectively degenerate in aged homo sapiens following 16 syndromic presentations: (1) Parkinsonism: nigrostriatal control for fast automatic movements of hand, larynx, bipedal posture and gait ("simian gait and hand"). (2) Frontal (highest level) gait disorders (lower body parkinsonism, gait apraxia, retropulsion): prefrontostriatal executive control of bipedal locomotion. (3) ataxia: new synergistic coordination of bipedal gait and fine motility. (4) Dyskinesias (chorea, dystonia, tremor...): intrusions of simian basal ganglia motor subroutines. (5) motoneuron diseases: new proximo-distal and bulbar motoneurones, preserving older ones (oculomotor, abdominal...). (6) Archaic reflexes: prefrontal disinhibition of old mother/tree-climbing-oriented reflexes (sucking, grasping, Babinski/triple retraction, gegenhalten), group alarms (laughter, crying, yawning, grunting...) or grooming (tremor=scratching). (7) Dysautonomia: contextual regulation (orthostatism...). (8) REM sleep disorders of new cortical functions. (9) Corticobasal syndrome: melokinetic control of hand prehension-manipulation and language (retrocession to simian patterns). (10) Frontal/temporal lobe degeneration: medial-orbitofrontal behavioural variant: self monitoring of internal needs and social context: apathy, loss of personal hygiene, stereotypia, disinhibition, loss of concern for consequences of acts, social rules, danger and empathy; dorsolateral executive variant: inadequacy to the context of action (goal, environmental changes...); progressive non-fluent aphasia: executive and praxic processing of speech; temporal variant: abstract concepts for speech, gestures and vision (semantic dementia, progressive nonfluent aphasia) (11) Temporomesial-limbic-paralimbic-associative cortical dementias (Alzheimer's disease, Lewy body, progressive amnesia): processing of explicit cognition: amnesic syndrome, processing of hand, larynx and eye: disorientation, ideomotor apraxia, agnosia, visuospatial processing, transcortical aphasia. (12) Focal posterior atrophy (Benson, progressive apraxia): visuomotor processing of what and where. (13) Macular degeneration: retinal "spot" for explicit symbols. (14) "Psychiatric syndromes": metacognition, self monitoring and regulation of hierarchical processing of metacognition: hallucinations, delusions, magic and mystic logic, delusions, confabulations; drive: impulsivity, obsessive-compulsive disorders, mental automatisms; social interactions: theory of mind, autism, Asperger. (15) Mood disorders: control on emotions: anxio-depressive and bipolar disorders, moria, emotional lability. (16) Musculoskeletal: inclusion body myositis: muscles for bipedal gait and fine motility. Paget's disease: bones for bipedal gait and cranium. Understanding of the genetic mechanisms underlying the evolution of these recent human brain regions and paleoneurology my be the key to the focal, asymmetrical or systemic character of neurodegeneration, the pathologic heterogeneity/overlap of syndromic presentations associating gait, hand, language, cognition, mood and behaviour disorders.
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PMID:Paleoneurology: neurodegenerative diseases are age-related diseases of specific brain regions recently developed by Homo sapiens. 1870 90

Succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder of GABA degradation with subsequent elevations in brain GABA and GHB, is a neurometabolic disorder with intellectual disability, epilepsy, hypotonia, ataxia, sleep disorders, and psychiatric disturbances. Neuroimaging reveals increased T2-weighted MRI signal usually affecting the globus pallidus, cerebellar dentate nucleus, and subthalamic nucleus, and often cerebral and cerebellar atrophy. EEG abnormalities are usually generalized spike-wave, consistent with a predilection for generalized epilepsy. The murine phenotype is characterized by failure-to-thrive, progressive ataxia, and a transition from generalized absence to tonic-clonic to ultimately fatal convulsive status epilepticus. Binding and electrophysiological studies demonstrate use-dependent downregulation of GABA(A) and (B) receptors in the mutant mouse. Translational human studies similarly reveal downregulation of GABAergic activity in patients, utilizing flumazenil-PET and transcranial magnetic stimulation for GABA(A) and (B) activity, respectively. Sleep studies reveal decreased stage REM with prolonged REM latencies and diminished percentage of stage REM. An ad libitum ketogenic diet was reported as effective in the mouse model, with unclear applicability to the human condition. Acute application of SGS-742, a GABA(B) antagonist, leads to improvement in epileptiform activity on electrocorticography. Promising mouse data using compounds available for clinical use, including taurine and SGS-742, form the framework for human trials.
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PMID:Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men. 1917 12

The Taiep rat is a myelin mutant with a motor syndrome characterized by tremor, ataxia, immobility, epilepsy, and paralysis. The rat shows a hypomyelination followed by a progressive demyelination. During immobilities taiep rats show a REM-like sleep pattern and a disorganized sleep-wake pattern suggesting taiep rats as a model of narcolepsy-cataplexy. Our study analyzed the role of postsynaptic serotonin receptors in the expression of gripping-induced immobility episodes (IEs) in 8-month-old male taiep rats. The specific postsynaptic serotonin agonist +/-1-(2,5-dimethoxy-4-iodoamphetamine hydrochloride (+/-DOI) decreased the frequency of gripping-induced IEs, but that was not the case with alpha-methyl-serotonin maleate (alpha-methyl-5HT), a nonspecific postsynaptic agonist. Although the serotonin antagonists, ketanserine and metergoline, produced a biphasic effect, first a decrease followed by an increase with higher doses, similar effects were obtained with a mean duration of gripping-induced IEs. These findings correlate with the pharmacological observations in narcoleptic dogs and humans in which serotonin-reuptake inhibitors improve cataplexy, particularly in long-term treatment that could change the serotonin receptor levels. Polysomnographic recordings showed an increase in the awakening time and a decrease in the slow wave and rapid eye movement sleep concomitant with a decrease in immobilities after use of +/-DOI, this being stronger with the highest dose. Taken together, our results show that postsynaptic serotonin receptors are involved in the modulation in gripping-induced IEs caused by the changes in the organization of the sleep-wake cycle in taiep rats. It is possible that specific agonists, without side effects, could be a useful treatment in human narcoleptic patients.
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PMID:Serotonergic-postsynaptic receptors modulate gripping-induced immobility episodes in male taiep rats. 1948 23

A 15-year-old girl had no REM sleep presumably due to a pontine cavernous hemangioma was reported. Her brain MRI revealed a cavernous hemangioma extending from the dorsal pontine to the medulla. She manifested truncal ataxia, facial nerve palsy, and ocular motor apraxia. She could not sleep in the supine position due to the sleep apnea accompanied with loud snoring. Overnight polysomnography (PSG) was performed for detection of obstructive sleep apnea syndrome (OSAS). In addition to severe OSAS and Cheyne-Stokes-like respiration at wake after sleep onset, her 1st PSG study revealed no periods with rapid eye movement, EEG characteristic of REM sleep, atonia and variation on respiratory and heart rate. Even after effective therapy for OSAS with non-invasive positive airway pressure ventilation (NPPV), her 2nd PSG also failed to show stage REM. These findings suggest that this pontine cavernous hemangioma disturbed her REM-on system. This is the first report of an individual with long-term loss of REM sleep and a valuable case for the understanding of anatomical structures of the REM-on system and the role of REM in memory consolidation.
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PMID:[Deficiency of REM sleep in a patient with pontine cavernous hemangioma]. 1976 54

Voltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of transient depolarizing currents and play a critical role in the electrical signaling between neurons. A null mutation in the VGSC gene SCN8A, which encodes the transmembrane protein Na(v)1.6, was identified previously in a human family. Heterozygous mutation carriers displayed a range of phenotypes, including ataxia, cognitive deficits, and emotional instability. A possible role for SCN8A was also proposed in studies examining the genetic basis of attempted suicide and bipolar disorder. In addition, mice with a Scn8a loss-of-function mutation (Scn8a(med-Tg/+)) show altered anxiety and depression-like phenotypes. Because psychiatric abnormalities are often associated with altered sleep and hormonal patterns, we evaluated heterozygous Scn8a(med-jo/+) mutants for alterations in sleep-wake architecture, diurnal corticosterone levels, and behavior. Compared with their wild-type littermates, Scn8a(med-jo/+) mutants experience more non-rapid eye movement (non-REM) sleep, a chronic impairment of REM sleep generation and quantity, and a lowered and flattened diurnal rhythm of corticosterone levels. No robust differences were observed between mutants and wild-type littermates in locomotor activity or in behavioral paradigms that evaluate anxiety or depression-like phenotypes; however, Scn8a(med-jo/+) mutants did show enhanced spatial memory. This study extends the spectrum of phenotypes associated with mutations in Scn8a and suggests a novel role for altered sodium channel function in human sleep disorders.
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PMID:Dysfunction of the Scn8a voltage-gated sodium channel alters sleep architecture, reduces diurnal corticosterone levels, and enhances spatial memory. 2035 42


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