Brainstem reflexes and brainstem auditory evoked responses in Huntington''s chorea.

Blink reflex, corneal reflex, jaw reflex, exteroceptive suppression in masseter muscles and brainstem auditory evoked potentials were measured in 20 patients with Huntington's chorea and 12 controls. A significantly increased latency of the second component of the homolateral and heterolateral blink reflex was found in the patient group as compared with the controls. The other investigations revealed no significant differences between patients and controls except for some facilitation of the jaw reflex in the patient group. Increase of second component latency of the blink reflex in the presence of normal corneal reflexes is suggestive of functional impulse conduction disturbance in the lower brainstem. It is discussed whether in Huntington's chorea this is to be attributed to alterations of cortical or striatal influence or to local brainstem abnormalities.     

Early detection of Huntington''s disease. Blink reflex and levodopa load in presymptomatic and incipient subjects.

The R2 response on the blink reflex was found to be abnormal in seven out of 17 Huntington's disease descendants. Such abnormalities were present in four untreated subjects and in three further subjects after administration of a single oral dose of levodopa-carbidopa. An increase in latency and differential latency (four cases), or in a single one of these parameters (three cases) were the abnormalities found, resembling findings in four incipient cases detected during routine family surveys. Continuous administration of levodopa-carbidopa over a 10-20 day period did not induce new characteristics in the blink reflex, nor increase those detected previously, and no case developed chorea. We suggest that the analysis of the blink reflex after a single oral levodopa-carbidopa dosage could provide an objective and quantifiable method for the detection of individuals at risk for Huntington's disease.     

Correlation between facial involuntary movements and abnormalities of blink and corneal reflexes in Huntington's chorea

Blink and corneal reflexes were studied in 11 patients with Huntington's chorea and the results compared with the severity of the disease. The latency of the R2 component of the blink reflex was delayed and the duration of R2 and of the corneal reflex (CR) prolonged. A greater habituation of the R2 component was found in the patients with involuntary movements in the face, and in some patients a long-lasting depression of R2 was present. A correlation was found between: (a) severity of involuntary face movements and R2 and CR latency and (b) severity of involuntary movements in the neck and latency of R2.     

Habituation of the orbicularis oculi reflex in dementia and dyskinetic states.

The habituation index is a quantitative expression of the ability of the orbicularis oculi (blink reflex) to adapt to a series of electrical stimuli applied to the supraorbital region. This parameter has been studied in a group of normal control subjects, and the results compared with those in cases of idiopathic and drug-induced Parkinsonism, states of dementia, and dyskinesias such as Huntington's chorea and senile chorea. Patients with Huntington's chorea showed a tendency for the reflex to habituate readily in contrast to patients with dementia caused by cortical atrophy and those with Parkinson's disease. Younger patients with Huntington's chorea had indices within the normal range. It seems unlikely that this test will prove of value in the detection of clinically unaffected relatives. Where dementia was associated with a reversible intracranial lesion, the habituation index was studied before and after treatment. Failure of habituation in this condition appears to be due to the release of a primitive protective reflex.     

Horizontal and vertical saccadic eye movement abnormalities in Huntington's chorea

With a newly developed infrared reflection technique, voluntary saccadic eye movements (VOLS), visually evoked saccades (VES) and unsuppressed visually evoked reflex saccades (USVERS) were measured in 11 patients with Huntington's chorea. Abnormalities, including latency increase, peak velocity decrease and undershoot dysmetria with multiple step saccades were found in all types of saccadic eye movements. Peak velocity decrease and undershoot dysmetria can be explained by dysfunction of the brainstem reticular formation in Huntington's chorea. USVERS and square wave jerks occurred abnormally frequently and showed direction-dependent differences. Both were more frequent in horizontal than in vertical direction. Frequency of USVERS and square-wave jerks tended to be correlated. These findings point to disinhibited superior colliculi as a possible common supranuclear origin of USVERS and square-wave jerks in Huntington's chorea.     

Features of the blink reflex in individuals at risk for Huntington's disease.

The aim of the study was to correlate the features of the blink reflex (BR) with the genetic abnormalities and the clinical findings in patients with Huntington's disease (HD) and asymptomatic gene carriers. Twenty patients with HD and 20 relatives were studied. Mutation analysis was performed for the CAG expansion within the HD gene using HD 333-HD 447 as oligonucleotide primers. The BR was elicited transcutaneously by electrical stimulation of the right supraorbital nerve. The recovery curve of the R2 and R3 responses after a conditioning stimulus was evaluated. R2 latency and duration and R3 duration were significantly increased in HD patients and in presymptomatic carriers in comparison with controls; reduced R2 recovery was also clear in both HD and gene-carrier relatives. In HD patients, the R2 latency increase correlated significantly with the severity of facial chorea. The R2 abnormalities are probably caused by impaired suprasegmental control by the basal ganglia over brainstem interneurons, which may precede the onset of involuntary movements, probably conditioning the severity of facial chorea during development of the disease.     

Masseter inhibitory reflex in movement disorders. Huntington's chorea, Parkinson's disease, dystonia, and unilateral masticatory spasm.

Evoked by electrical stimulation of the mental nerve, the masseter inhibitory reflex consists of an early and a late silent period (SP1 and SP2), which interrupt the voluntary electromyographic (EMG) activity in the masseter muscle. We recorded the masseter inhibitory reflex and measured its latency, depth of suppression, duration and recovery cycle to paired stimuli, in patients with Huntington's chorea. Parkinson's disease, dystonia, or unilateral masticatory spasm. In patients with Huntington's chorea the reflex data and recovery cycle were normal. In patients with Parkinson's disease or dystonia, although the reflex data were normal, SP2 recovered far more rapidly than it did in control subjects. This is possibly due to hypoactivity of an inhibitory control of the polysynaptic chain of ponto-medullary interneurons that mediate SP2. In patients with unilateral masticatory spasm, both SP1 and SP2 were absent. Suppression is probably absent because this involuntary movement originates at a point along the peripheral course of the nerve.     

Maturation of blink reflex in children

The blink reflex was examined in 57 subjects aged from neonate to adult in the alert state. The ipsilateral late response (R2) was elicited in all subjects and considered most suitable to evaluate maturational changes of the blink reflex. In a few subjects older than 3 years and of adults, the ipsilateral early response (R1) was difficult to observe. The contralateral late response (R2') could not be obtained in 32% of neonates and infants. From the observation about developmental change of an interference pattern, a latency shortening of R2 and a latency difference between R2' and R2, the blink reflex in children may be considered as mature at no later than 5 years of age. In addition, the R2 latency tended to increase temporarily through 1 or 2 years from late infancy. The reflex circuit evaluated by the blink reflex in children may partially change its makeup after the early infantile period and is almost fully mature at no later than 5 years.     

The corneal reflex and the R2 component of the blink reflex

A reflex contraction of the human orbicularis oculi muscles can be evoked by stimulation of either the supraorbital region ("blink reflex") or the cornea ("corneal reflex"). We found that the latency of the corneal reflex was longer, and the duration was longer than the R2 component of the blink reflex. The absolute refractory period of the R2 component of the blink reflex was longer after supraorbital than after corneal conditioning stimulation. When the R2 component of the blink reflex was habituated by repetitive stimuli, stimulation of the cornea still evoked a reflex, but supraorbital stimulation produced only a depressed R2 response. These findings suggest that the two reflexes do not have identical neural connections.     

Blink reflex in facial-hypoglossal anastomosis

Summary The blink reflex was investigated in two patients after a facial-hypoglossal anastomosis had been performed. In each case the first component of the blink reflex could be demonstrated with normal latency on the operated side after ipsilateral supraorbital stimulation. These findings give further evidence that the first component of the blink reflex is not monosynaptic in nature. The second component of the blink reflex was distinctly retarded in the first case and was not seen at all in the second case. The second component of the blink reflex is influenced strongly by alteration of the intrabulbar and efferent part of the reflex circuits; it shows some correlation with voluntary motor activity.Stipendiary of the Humboldt Foundation.     

Corneal reflex in normal and pathological subjects

The orbicularis oculi response can be evoked both by mechanical stimulation of the cornea (corneal reflex) and by electrical stimulation of the skin overlying the supraorbital nerve (blink reflex). Mechanical stimuli to the cornea activate A delta and C free nerve endings of the corneal mucosa. Electrical stimuli to the supraorbital nerve activate A beta, A delta and C fibers of the nerve trunk. Both reflexes present a bilateral late response, but the blink reflex shows in addition an early ipsilateral component (R1), which has never been observed with the corneal stimulation in man. We have developed a simple technique of electrical stimulation of the cornea which provides stable responses and allows precise measurements of threshold and latency of the reflex. In normal subjects, the threshold ranged from 50 to 350 microA, and the maximal stimulus that the subject could bear (tolerance level) ranged from 1000 to 2500 microA. The minimal latency to tolerance level stimuli was 39 +/- 3 msec. The latency difference between the direct responses evoked from the two opposite corneas never exceeded 8 msec and the difference between the direct and consensual responses elicited from the same cornea never exceeded 5 msec. An early ipsilateral component similar to the R1 response of the blink reflex was not observed, even with supramaximal stimulation. The electrically evoked corneal reflex was normal in 10 cases of essential trigeminal neuralgia, while the responses showed significant abnormalities in 18 subjects submitted to thermocoagulation of the Gasserian ganglion as a treatment of neuralgic pain, as well as in 2 cases of symptomatic neuralgia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blink reflex measurement of effects of trichloroethylene exposure on the trigeminal nerve.

Trichloroethylene (TCE) exposure is known to have specific toxic effects on cranial nerves, the trigeminal nerve (V) in particular. The electrophysiological measurement of the blink reflex (BR) can quantify latency changes in the Vth and VIIth cranial nerve reflex arc. Prior study looked at the blink reflex measurement in a community group exposed to TCE in their drinking water. This study evaluated the use of the electrophysiologic blink reflex as an indicator of neurotoxic effects of TCE in occupationally exposed workers. The BR was tested in individual cases with documented histories of exposure to known chemical neurotoxins including TCE (n = 18). When compared with the nonexposed laboratory control values (n = 30), the subjects with a significant history of TCE exposure demonstrated the most prolonged latencies (greater than or equal to 3.0 SD above the nonexposed group mean) in the R1 component of the blink reflex measurement. The electrophysiological study of the blink reflex has application in assessing TCE exposure and in documenting the neurotoxic effects of that exposure on trigeminal nerve functions in humans.     

A blinded study of the suppressibility of involuntary movements in Huntington's chorea, tardive dyskinesia, and L-dopa-induced chorea

Videotapes of patients with Huntington's chorea, tardive dyskinesia (TD), and L-DOPA-induced chorea in Parkinson's disease were taken while the patients were seated with their legs dangling. The videotapes were scored in a blinded fashion for suppressibility of dyskinesias. Most patients with TD or L-DOPA-induced chorea substantially suppressed their involuntary movements, whereas most patients with Huntington's chorea did not. There was a small overlap between the TD and Huntington's chorea groups and suppressibility therefore could not absolutely distinguish between them. Suppressibility testing may nonetheless be a valuable clinical tool since a good, excellent, or complete suppressibility rating was highly suggestive of TD but not Huntington's chorea. TD and L-DOPA-induced chorea may be more pathophysiologically similar to each other than either is to Huntington's chorea.     

A study of blink reflex in person with severely handicapped]

1) We evaluated blink reflex from 50 cases of severe handicapped. 7 cases (14%) had normal blink reflex. Abnormality of prolonged latency or no response of blink reflex was much more easily seen on R2 and R2' than R1, and dysfunction of spinal trigeminal complex or bulbar reticular formation might be existed in those cases. 2) We found abnormal blink reflex had some relationship with mental disturbance or bulbar function. Result of ABR and head CT also suggested that some kinds of cerebral factors might influenced to blink reflex of severe handicapped cases. 3) Blink reflex was one of the useful records for severe handicapped patients to evaluated underline pathogenesis of brain stem function.     

Electrically and mechanically elicited blink reflexes in infants and children--maturation and recovery curves of blink reflex.

We studied the electrically and mechanically elicited blink reflexes in 2 groups of subjects, i.e., 237 newborn infants, 25-41 weeks of conceptional age, and 74 children, 1 month-12 years of age. In infants after 25 weeks of conceptional age we could usually induce the early response (R1) and ipsilateral late response (R2), while the contralateral late response (R2') of the electrical blink reflex became apparent after 33 weeks of conceptional age and the frequency of the appearance of R2' reached more than 60% after 38 weeks of conceptional age. After 7 months of age, R2' was usually observed. The R1 latency in full-term newborns was close to adult values, while the R2 and R2' latencies reached adult values at 7-12 years. After 1 year of age the latency of the R2 mechanical blink reflex had a tendency to be shorter than that of the electrical blink reflex. Under 35 weeks of conceptional age, the recovery curves of the blink reflex were considerably different from those of full-term infants, and premature infants showed little or no evidence of inhibition. These results indicate the absence of inhibitory interneurones in premature infants.     

Reflex arc of the first component of the human blink reflex: a single motoneurone study.

Latency variation of consecutive responses of single orbicularis oculi motoneurones in the first component of the electrically elicited blink reflex was 2.6 times larger than that of the H reflex of the soleus muscle fibres. Some motoneurones showed bimodal latency distribution or double responses or both at an interval of about 4-5 ms. Typical first component responses were sometimes obtained by contralateral stimulation. Central conduction time in the brainstem, estimated for 15 motoneurones, was between 2.4 and 6.6 ms. It is concluded that the first component of the blink reflex is conducted through an oligosynaptic arc including one or more interneurones.     

Platelet dopamine uptake in Huntington's chorea and Gilles de la Tourette's syndrome: effect of haloperidol.

Uptake of 14C-dopamine by human platelets has been studied in two diseases, namely Gilles de la Tourette's syndrome and Huntington's chroea, in which abnormal metabolism of dopamine has been implicated. Platelets from untreated Huntington's chorea patients showed a small increase in Km and Vmax.; platelets from patients in all other groups showed an uptake identical with the controls. Haloperidol (10(-5)M) was also shown to be a strong non-competitive inhibitor of 14C-DA uptake by platelets. This property is probably unrelated to the drugs' action in ameliorating the symptoms of Huntington's chorea which is likely related to the increase in cholinergic neuronal activity produced by neuroleptic blockade of dopamine receptors.     

Study of the excitability cycle of the blink reflex in Huntington's chorea.

The trigemino-facial reflex was studied in 7 patients affected by Huntington's chorea and in 10 patients affected by Parkinson's disease. The results show a different behavior of the habituation phenomenon in the two groups of patients: it is enhanced in the choreic and abolished in the parkinsonian patients. The main changes concern the time course of the second phase (the first inhibitory phase) of the reflex excitability cycle, in fact, the inhibitory phase appears very pronounced and prolonged in huntingtonian patients and reduced or abolished in parkinsonian patients. Some pathophysiological mechanisms involved in the control of the trigeminofacial reflex excitability are discussed with particular regard to the role of the hemispheric structures.     

Pathophysiology of chorea and bradykinesia in Huntington's disease.

This article reviews the neurophysiological abnormalities described in Huntington's disease. Among the typical features of choreic movements are variable and random patterns of electromyographic (EMG) activity, including cocontraction of agonist and antagonist muscles. Studies of premotor potentials show that choreic movements are not preceded by a Bereitschaftspotential, therefore demonstrating that choreic movement is involuntary. Early cortical median-nerve somatosensory-evoked potentials have reduced amplitudes and the reduction correlates with reduced glucose consumption in the caudate nucleus. Long-latency stretch reflexes evoked in the small hand muscles are depressed. These findings may reflect failed thalamocortical relay of sensory information. In Huntington's disease, the R2 response of the blink reflex has prolonged latencies, diminished amplitudes, and greater habituation than normal. These abnormalities correlate with the severity of chorea in the face. Patients with Huntington's disease perform simple voluntary movements more slowly than normal subjects and with an abnormal triphasic EMG pattern. Bradykinesia is also present during their performance of simultaneous and sequential movements. Eye movements show abnormalities similar to those seen in arm movements. In Huntington's disease, arm movement execution is associated with reduced PET activation of cortical frontal areas. Studies using transcranial magnetic stimulation show that patients with Huntington's disease have normal corticospinal conduction but some patients have a prolonged cortical silent period. Bradykinesia results from degeneration of the basal ganglia output to the supplementary motor areas concerned with the initiation and maintenance of sequential movements. The coexisting hyperkinetic and hypokinetic movement disorders in patients with Huntington's disease probably reflect the involvement of direct and indirect pathways in the basal ganglia-thalamus-cortical motor circuit.     

Altered growth hormone release in Huntington''s chorea.

Glucose tolerance tests have been performed on five patients with Huntington's chorea and no difference in response has been observed compared with seven controls. Insulin tolerance tests have been performed on 12 patients with Huntington's chorea and 10 controls. Blood samples were taken at regular intervals for 75 minutes and analysed for blood glucose, insulin, and growth hormone (HGH). There was no difference between the groups in the hypoglycaemia which developed. The patients, however, had an earlier elevation of HGH than the controls. The difference was highly significant (P less than 0.001, P less than 0.02) 30 and 35 minutes after the intravenous injection of insulin. The patients, although awake, ceased to have choreiform movements for at least the last 60 minutes of the insulin tolerance tests. Our observations of HGH release imply that hypothalamic activity is altered in Huntington's chorea. Further observations of HGH release may therefore be of value in its diagnosis.