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Cough associated with angiotensin-converting enzyme inhibitors.

Cough is reported by between 0.7% and 14% of patients taking angiotensin-converting enzyme (ACE) inhibitors. There are more reports from women and non-smokers. The development of cough during ACE inhibitor therapy is associated with a reversible increase in the response of the cough reflex. The response remains normal in those who do not develop cough while on ACE inhibitor therapy. Both hypersensitivity of the cough reflex and the symptom of cough are reversed by sulindac which suggests that the abnormal reflex is dependent on cyclo-oxygenase products.

Angiotensin-Converting Enzyme Inhibitors↗

Symptomatic and essential palatal tremor. 1. Clinical, physiological and MRI analysis.

Palatal tremor (brief, rhythmic involuntary movements of the soft palate) apparently comprises two different nosological entities: essential palatal tremor (EPT) and symptomatic palatal tremor (SPT). The site of the abnormality in EPT is unknown, whereas SPT is believed to arise from a lesion of the brainstem or cerebellum (within the Guillain-Mollaret triangle). The clinical and physiological properties of these conditions were studied in four patients with EPT and six patients with SPT. Patients with EPT had normal cerebellar function, but those with SPT had clinical signs of cerebellar dysfunction. The palatal movements were consistent with activation of the tensor veli palatini muscle in EPT and of the levator veli palatini muscle in SPT. During sleep, EPT stopped, whereas SPT continued with only slight variations in the tremor rate. The cycle of palatal tremor could not be reset by stimulation of trigeminal afferents in either EPT or SPT patients, and Valsalva's manoeuvre did not consistently affect the rhythm of the tremor in either group. The palatal tremor cycle exerted remote effects on the tonic electromyographic activity of the upper and lower extremities only in patients with SPT. These effects were present only on the side of the cerebellar signs (opposite the side with the enlarged inferior olive) in patients with a unilateral syndrome. Essential palatal tremor patients had only polysynaptic brainstem reflex abnormalities, whereas SPT patients had abnormalities of monosynaptic, oligosynaptic and polysynaptic brainstem reflexes. Magnetic resonance imaging showed no evidence of structural abnormalities in EPT patients, but SPT patients had a hyperdense signal of the ventral upper medulla (the region of the inferior olive) on T2-weighted images. These observations support the hypothesis that EPT and SPT are two different diseases. In SPT, cerebellar dysfunction ipsilateral to the palatal tremor may be due, in part, to abnormal function of the contralateral hypertrophic inferior olive. The proposed basis of SPT is a disturbance of electrotonic coupling between the cells of the inferior olive induced by a lesion of the dentato-olivary pathway. Similar mechanisms could be responsible for postural tremors in general. The pathophysiological basis of EPT remains unknown.

Adult↗

Sensory neuropathy of the trigeminal, glossopharyngeal, and vagal nerves in Sjögren's syndrome.

Isolated cranial nerve involvement in primary Sjögren's syndrome (primary SS) has rarely been described. We report the case of a patient with sensory neuropathy of the trigeminal and also the glossopharyngeal and vagal nerves, which has not been identified previously. The electrophysiological findings in our patient with primary SS confirmed trigeminal sensory neuropathy with abnormal blink reflexes and abnormal cutaneous masseter inhibitory reflexes.

Cranial Nerve Diseases↗

Morphological and behavioral markers of environmentally induced retardation of brain development: an animal model.

In most neurotoxicological studies morphological assessment focuses on pathological effects, like degenerative changes in neuronal perikarya, axonopathy, demyelination, and glial and endothelial cell reactions. Similarly, the assessment of physiological and behavioral effects center on evident neurological symptoms, like EEG and EMG abnormalities, resting and intention tremor, abnormal gait, and abnormal reflexes. This paper reviews briefly another central nervous system target of harmful environmental agents, which results in behavioral abnormalities without any qualitatively evident neuropathology. This is called microneuronal hypoplasia, a retardation of brain development characterized by a quantitative reduction in the normal population of late-generated, short-axoned neurons in specific brain regions. Correlated descriptive and experimental neurogenetic studies in the rat have established that all the cerebellar granule cells and a very high proportion of hippocampal granule cells are produced postnatally, and that focal, low-dose X-irradiation either of the cerebellum or of the hippocampus after birth selectively interferes with the acquisition of the full complement of granule cells (microneuronal hypoplasia). Subsequent behavioral investigations showed that cerebellar microneuronal hypoplasia results in profound hyperactivity without motor abnormalities, while hippocampal microneuronal hypoplasia results in hyperactivity, as well as attentional and learning deficits. There is much indirect clinical evidence that various harmful environmental agents affecting the pregnant mother and/or the infant lead to such childhood disorders as hyperactivity and attentional and learning disorders. As the developing human brain is more mature at birth than the rat brain, the risk for microneuronal hypoplasia and consequent behavioral disorders may be highest at late stages of fetal development, in prematurely born and small-for-weight infants, and during the early stages of infant development. Recent technological advances in brain imaging techniques make it possible to test this hypothesis and to assess the possible relationship between the degree of retarded brain development and ensuing behavioral disorders.

Animals↗

A comparison of newborns' NBAS reflex responses using total and individual scores. Neonatal Behavioral Assessment Scale.

The purpose of this study was to compare results found using a total summative score of abnormal reflex responses with the results found using individual reflex scores. The 20 reflexes included as part of the Brazelton Neonatal Behavioral Assessment Scale (NBAS) were assessed on 196 neonates on the 1st and 2nd days postnatally. Differences due to of type of delivery, birth weight, whether their mothers were insulin-dependent diabetics or nondiabetics, and day of testing were assessed by using analysis of variance. The key results were that all effects found using the total reflex score were replicated with individual reflex scores and that individual reflex scores also revealed effects not shown using the total score. It was concluded that the individual reflex scores, rather than the total score, should be used when evaluating newborn reflex performance.

Adult↗

Behavioral characterization in a comprehensive mouse test battery reveals motor and sensory impairments in growth-associated protein-43 null mutant mice.

The growth-associated protein (GAP)-43 is a major neuronal protein associated with axonal growth, neuronal plasticity and learning. The observation that only 5-10% of mice with a full GAP-43 gene deletion survive weaning suggests that basic neural functions are disturbed. Here we used a comprehensive test battery to characterise and quantify the motor and sensory function of surviving adult homozygous GAP-43 (-/-) mice as compared with GAP-43 (+/-) and wild-type animals. The test battery was comprised of motor, sensory, and reflex tests producing 25 measures of locomotion, as well as epicritic, auditory, olfactory and visual function. The analysis revealed significant impairments in muscle strength, limb coordination and balance in GAP-43 (-/-) mice. Furthermore, GAP-43 (-/-) animals were hyperactive and showed reduced anxiety as measured by open field and light dark tests. In sensory tests, GAP-43 (-/-) mice were tested for impaired tactile and labyrinthine function. Abnormal reflexes were found in the contact and vibrissa placing responses, and in the crossed extensor reflex. GAP-43 (+/-) animals showed only moderate abnormalities as compared with wild-type animals. We conclude that GAP-43 is necessary for the development and function of a variety of neuronal systems. The results also show that the comprehensive test battery used in the present study represents a sensitive approach to assess the functional integrity of ascending and descending pathways in genetically manipulated mice.

Analysis of Variance↗

Variable relationship between peripheral somatic and autonomic neuropathy in patients with different syndromes of diabetic polyneuropathy.

The relationship between abnormal peripheral nerve electrophysiology and abnormal cardiovascular autonomic function has been studied in four groups of diabetic subjects, comparable with regard to age, duration, and type of diabetes. Thirty-three had no symptoms of neuropathy, 28 had newly developed painful neuropathy, 24 had chronic painful neuropathy, and 21 had painless neuropathy with associated recurrent foot ulcers. In all three symptomatic groups, electrophysiology and autonomic function were more abnormal than in asymptomatic diabetic subjects. There was a significant overall relationship between peripheral nerve (electrophysiologic) and autonomic (cardiovascular reflex) dysfunction. However, when considered by groups, the degree of cardiovascular reflex abnormality was similar in the three symptomatic groups, whereas electrophysiology was appreciably worse in the foot ulcer group than in patients with painful neuropathy. Thus, patients with painful neuropathy had a higher ratio of autonomic (small fiber) abnormality to electrophysiologic (large fiber) abnormality. By contrast, foot ulceration was associated with the worst electrophysiologic (large fiber) abnormality. Heavier alcohol consumption and more severe retinopathy were also related to foot ulceration. In diabetic subjects with symmetrical sensory neuropathy, the relationship between large fiber and small fiber damage is not uniform. We conclude that there may be different etiologic influences on large and small fiber neuropathy in diabetic subjects and that the predominant type of fiber damage may determine the form of the presenting clinical syndrome.

Adult↗

[Reflex dystrophy after reconstruction of the axillary artery].

Reflex sympathetic dystrophy (RSD) is a complex syndrome of pain, trophic changes and vasomotor instability affecting the limbs. Numerous theories have been suggested to explain the pathophysiology. None is universely accepted. In most of the patients reported, an antecedant event such as trauma or surgery is implicated in the initiation of symptoms. We describe a case of reflex sympathetic dystrophy developing after reconstruction of a. axillaris. To our knowledge there have only been a few previous descriptions of reflex dystrophy following vascular surgery. The mechanism of reflex sympathetic dystrophy secondary to vascular trauma is discussed. Presumely, damage to the arterial wall by trauma may initiate abnormal reflex activity and lead to RSD. We suggest that vascular surgery should be considered as a potential risk factor for the development of RSD.

Arterial Occlusive Diseases↗

Stapedius reflex in the monitoring of NaF treatment of subclinical otosclerosis.

Stapedius reflex testing was utilized to monitor the progression of subclinical otosclerosis and evaluate the efficacy of NaF treatment in stabilizing the disease process. The investigation was performed on 93 relatives of patients suffering with surgically confirmed otosclerosis. Subjects were divided into two groups. The first group was treated with NaF in doses ranging from 6 to 16 mg in relation to age. The treatment lasted two years. The second group served as control subjects. Before entering the research, all subjects presented reflex abnormalities represented by a partial or complete on-off effect in one or both ears. Changes in stapedius reflex morphology (from partial to complete on-off and from complete on-off to absence of the reflex) were evaluated at 1 and 2 years. The groups had not developed significant differences at 1 year. At 2 years, the incidence of stable stapedius reflex findings was 91.5% in the treated ears and 77% in the control group. The difference is significant (p less than 0.05) and indicates a stabilizing effect of NaF on the disease process.

Acoustic Impedance Tests↗

[Untreatable hiccup as un unusual sign in a rostral occlusion syndrome of the basilar artery].

Hiccoughs (singultus) is a habitual physiological phenomenon, the persistence of which might indicate neurological and extraneurological multiple lesions. Its activation involves starting up numerous central and peripheral mechanisms which have yet to be clearly determined. Hiccoughs results from an intermittent myoclonus of the diaphragm, reflex in origin, with unknown authentic cause or physiological significance. It has been suggested that, more than just an abnormal reflex, it could be a type of myoclonus brought on by repeated activity of the 'solitary inspiratory nucleus', by releasing control of the inhibiting-activating upper nervous system activity. We present the case of a patient with uncontrollable hiccoughs lasting over six years as a result of paramedial bilateral thalamic ischaemia (rostral occlusion syndrome of the basilar artery type 1) of cardioembolic origin (auricular fibrillation) secondary to hyperthyroidism.

Administration, Oral↗

Galvanic evoked vestibulospinal and vestibulocollic reflexes in stroke.

OBJECTIVE: Following stroke, the startle reflex, mediated via the reticulospinal tract, is often facilitated. Vestibulospinal reflexes are another bulbospinal reflex, abnormalities of which may contribute to impaired body posture and stance following stroke. We recorded galvanic evoked vestibulospinal and vestibulocollic reflexes to assess whether these showed similar changes to those for startle following stroke affecting the pons and above. METHODS: Twenty-four stroke subjects (aged 40-82) were studied in the vestibulospinal part of the study, 21 stroke subjects (aged 40-81 years) were studied in the vestibulocollic part, including 18 studied in both. Transmastoid galvanic (DC) current was used to stimulate the vestibular nerve. Vestibulocollic responses were recorded from the sternocleidomastoid muscles and vestibulospinal responses from over soleus in standing subjects. RESULTS: Vestibulocollic reflex amplitudes and latencies showed no significant differences between the two sides. Similarly short latency (SL) and medium latency (ML) vestibulospinal reflexes did not differ significantly in frequency, latency or amplitude between the affected and unaffected legs. CONCLUSIONS: Vestibular reflexes are not facilitated by stroke at or above the pontine level. The exaggeration of startle by stroke may be specific to this reflex.

Adult↗

Acute and chronic adaptations of muscle proprioceptors in response to increased use.

Acute adaptations to use have been shown to occur in both the muscle spindle and Golgi tendon organ pathways. This short term activation adaptation increases the excitability of the motoneuron pool, thereby potentially providing a nonvoluntary increase in the excitation of subsequent contractions. It is thought that the intrafusal muscle fibres reset to a higher gain after contraction and that the tendon organ pathway undergoes a brief desensitisation. These phenomena could be important clinically when trying to stretch muscles, i.e. a contraction before a stretch should make the stretch more difficult. Also, this could affect the amount of muscle force generated, thereby altering motor behaviours requiring fine accuracy. Research on the adaptations of proprioceptors during free movement, using locomotion as a model, has found that the hypothesis of consistent alpha-gamma coactivation during motor behaviours is much more complicated and adaptable, depending on the environmental circumstance and the specific motor task. These research findings support the use of selective training, i.e. training to the task, for optimal motor learning. The results of the relatively limited research on chronic adaptations of proprioceptors due to exercise has shown that on a microlevel, the intrafusal muscle fibres may show some metabolic changes but do not show any hypertrophy. However, on a more macro level, with extended training, the latency of the stretch reflex response is found to be decreased and the amplitude is found to be increased in both animals and humans. Through classical conditioning research, proprioceptors may also be necessary for motor learning. Lastly, both primates and humans have been shown to be able to up- or down-grade their stretch reflex responses using operant conditioning techniques and many practice sessions. These findings have important implications both for rehabilitation of persons with abnormal reflex activity and in the training of athletes. This review provides some consolidation of the recent research findings, but much more research needs to be done in order to fully understand the purpose and importance of the proprioceptive sensory system.

Humans↗

Cochlear otosclerosis: acoustic reflex findings.

Progressive cochlear impairment develops in a small percentage of patients with clinical otosclerosis, apparently owing to involvement of the cochlea by the otosclerotic bone. In recent years it has been postulated that otosclerosis frequently produces a pure sensorineural hearing impairment without stapedial involvement. We investigated the acoustic reflex responses in a group of patients diagnosed as sensorineural otosclerosis and compared these reflex findings with the findings in patients with confirmed otosclerosis but with a minimal conductive impairment. In the minimal conductive hearing impairment group we substantiated the findings of others that the negative on-off reflex is common in otosclerotic patients whose conductive impairment is 10dB or less. In the group with cochlear otosclerosis we found abnormal reflexes in 58 percent of the patients. These findings indicate that stapedial involvement is common in patients thought to have pure sensorineural otosclerosis.

Adolescent↗

Afferent limb of the human jaw reflex: electrophysiologic and anatomic study.

Jaw reflexes were recorded before and after neurosurgery of the trigeminal sensory root or the gasserian ganglion in 11 patients with idiopathic trigeminal neuralgia and in 2 patients with orbital malignancies. The reflex was also studied in three patients with unilateral midbrain lesions verified by postmortem findings. Jaw reflex abnormalities appeared in all cases, although there were no clinical or EMG signs of masseter dysfunction. Proprioceptive afferent fibers of the jaw reflex therefore seem to be mediated by the sensory and not the motor root. The afferent limb of the jaw reflex seems to run centrally through the midbrain, probably through the mesencephalic nucleus of the trigeminal nerve.

Adult↗

Stapedius reflex decay test in diagnosis of myasthenia gravis (MG).

Stapedius reflex decay test (SRDT) was attempted in 30 patients with suspected myasthenia gravis (MG). In 43% of the sample measurement of the decay was not possible because of an audiologic abnormality, reflex threshold too high for safe testing or absence of the reflex with no obvious cause. A control group of 24 normal subjects showed a large variance and thus only a decay, after 5 minutes of stimulation, greater than 50% of the original value was considered abnormal. Out of 17 patients in whom SR decay was successfully measured, 7 (41%) had an abnormal value. Sensitivity of the test was found at 80%, specificity at 75%, when the clinical diagnosis of MG, upheld in follow-up, was taken as a criterion. The percentage of concordant abnormal findings was 50% for repetitive electrical stimulation of a peripheral nerve, 60% for positive effect of anticholinesterase drugs, 100% for presence of ACh receptor antibodies.

Acoustic Impedance Tests↗

Autonomic neuropathy: diagnosis and impact on health in adolescents with diabetes.

Symptomatic autonomic neuropathy and abnormal cardiovascular autonomic tests are associated with increased mortality due to vascular disease and increased risk of sudden deaths. Intensive therapy in the DCCT caused a significant risk reduction of developing autonomic nerve abnormalities at five years only in the Primary Prevention Group (4 vs. 9%). At the Royal Alexandra Hospital for Children, the prevalence of cardiovascular reflex abnormalities is 28%. Over 5 years, we have found no increase in the rate of single cardiovascular abnormalities and a low rate of persistence. Two or more abnormalities developed in 5%. Repeated measures of pupillary function showed a significant increase in abnormalities and a higher level of persistently abnormal tests. Spectral analysis and 24-hour BP monitoring may detect autonomic dysfunction at earlier stages but longitudinal studies are not yet available.

Adolescent↗

Radiographic assessment of laryngeal reflexes in ketamine-anesthetized cats.

The competence of the laryngeal closure reflexes of cats anesthetized with ketamine was assessed. Radiographic evaluations of the respiratory and digestive tracts were made after colloidal barium suspension was instilled into the pharynges of conscious and ketamine-anesthetized cats. There was a significant ketamine dose-related response of spread of contrast medium into the supraglottic laryngeal area and into the stomach 2 minutes after contrast medium was instilled into the pharynx (P less than 0.05). Cats did not aspirate contrast medium into the lower respiratory tract. Three ketamine-anesthetized cats aspirated contrast medium into the subglottic area of the larynx, and 2 of these cats also aspirated the material into the cranial part of the trachea. This material was coughed up and swallowed within 5 minutes. Transit time of contrast medium into the stomach seemed to be increased in 11 of the 15 cats given the larger dosages of ketamine (24, 36, 48 mg/kg of body weight), compared with that in conscious cats and those given ketamine at 12 mg/kg. Competent laryngeal protective reflexes in cats can be maintained with ketamine anesthesia. Contrast radiography could be used as a diagnostic aid in ketamine-anesthetized cats suspected of laryngeal reflex abnormalities.

Animals↗

The oculo-auricular phenomenon. Findings in normals and patients with brainstem lesions.

The oculo-auricular phenomenon consists of bilateral coactivation of external ear muscles during lateral gaze. The electromyogram of the transverse auricular muscle was recorded in 25 healthy volunteers and 1186 patients. In normal subjects bilateral coactivation was observed with lateral gaze (96%), convergence (61%), active and intended head rotation (100%) and passive head rotation (50%). Uni- and bilateral labyrinthine excitation (60 and 80%) and proprioceptive input from the neck muscles (38%) are also effective. In patients with brainstem disease abnormal transverse auricular muscle coactivation is characterized by absence of activity in one or both ear muscles during lateral gaze in either or both directions. The most frequent abnormality was absence of transverse auricular muscle activity homolateral to right or left gaze (type Ia pattern). It was related to homolateral impairment of the blink reflex R1-response (90%) and the caloric response (90%), and to contralateral masseter reflex abnormality (70%). Electrophysiological data, clinical signs and imaging findings indicate that the type Ia pattern is caused by homolateral pontine or contralateral midbrain lesions. It is suggested that the supranuclear organization of the oculo-auricular phenomenon is based on descending tracts crossing at a mid-pontine level.

Brain Diseases↗