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PubMed2004

Hyperekplexia and stiff-man syndrome: abnormal brainstem reflexes suggest a physiological relationship.

BACKGROUND AND OBJECTIVES: Hyperekplexia and the stiff-man syndrome (SMS) are both conditions with exaggerated startle suggesting abnormal brainstem function. Investigation of brainstem reflexes may provide insight into disturbed reflex excitation and inhibition underlying these movement disorders. PATIENTS AND METHODS: Using four-channel EMG, we examined four trigeminal brainstem reflexes (monosynaptic masseter, masseter inhibitory, glabella, and orbicularis oculi blink reflexes) and their spread into pericranial muscles in five patients with familial hyperekplexia (FH), two with acquired hyperekplexia (AH), 10 with SMS, and 15 healthy control subjects. RESULTS: Both FH/AH and SMS patients had abnormal propagation of brainstem reflexes into pericranial muscles. All patients with hyperekplexia showed an abnormal short-latency (15-20 ms) reflex in the trapezius muscle with a characteristic clinical appearance ("head retraction jerk") evoked by tactile or electrical stimulation of the trigeminal nerve, but normal monosynaptic masseter reflexes. Inhibitory brainstem reflexes were attenuated in some FH/AH patients. Four of 10 patients with SMS had similar short-latency reflexes in the neck muscles and frequently showed widespread enhancement of other excitatory reflexes, reflex spasms, and attenuation of inhibitory brainstem reflexes. CONCLUSION: Reflex excitation is exaggerated and inhibition is attenuated in both stiff-man syndrome and familial or acquired hyperekplexia, indicating a physiological relationship. Reflex transmission in the brainstem appears biased towards excitation which may imply dysfunction of inhibitory glycinergic or GABAergic interneurons, or both.

Adolescent↗

PubMed1985

Hoffmann reflex variations produced by task demand characteristics.

It has been shown that monosynaptic reflexes could be facilitated or inhibited during tasks differing in nature. The amplitude of the Hoffmann reflex (H reflex) and heart rate have been studied during the performance of two versions of a mental task and a tracking task varying in degree of difficulty. Modification of the H reflex does not depend upon the nature of the task. A slight increase in cardiac rhythm and a facilitation of H reflex during easy tasks and a marked increase in cardiac rhythm associated with inhibition of H reflex during difficult tasks were observed. The increase in H reflex would be due to an activation of the reticular formation. The inhibition of motor response can be attributed to an effortful process which develops when the tasks become difficult.

Adult↗

PubMed1997

Selective depression of the spinal polysynaptic reflex by the NMDA receptor antagonists in an isolated spinal cord in vitro.

1. The effects of N-methyl-D-aspartate (NMDA) receptor glycine-binding site antagonists 7-chlorokynurenate (7-Clkyn) and (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966) on spinal reflexes in an isolated spinal cord that was maintained in Mg(2+)-free medium in vitro were examined. The actions of 7-Clkyn and HA-966 were compared with those of the channel-site antagonist (i.e., dizocilpine) and NMDA-binding site antagonists--that is, 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (CPP) and DL-2-amino-5-phosphonovalerate (APV). 2. 7-Clkyn and HA-966 produced a selective depression of the polysynaptic reflex (PSR) while negligibly affecting the activity of the monosynaptic reflex (MSR). The PSR was also differentially suppressed by dizocilpine, CPP and APV. The PSR inhibitory activity of the NMDA antagonists was in the following order: dizocilpine > CPP > APV = 7-Clkyn > HA-966. 3. The inhibitory effects of 7-Clkyn on PSR were markedly antagonized by the simultaneous application of D-serine, an agonist for the NMDA receptor glycine-binding sites. However, PSR inhibition by dizocilpine and CPP was unaffected. 4. Inhibition of the PSR by 7-Clkyn persisted in the presence of strychnine, which markedly increased the PSR activity by itself. 5. These findings suggest that the NMDA receptor glycine-binding sites play a role in generating the NMDA receptor-mediated PSR in the spinal cord in vitro.

Animals↗

PubMed2001

Changes in jaw reflexes by stimulation of the hypothalamus in anesthetized rabbits.

Changes in the masseteric monosynaptic reflex (MMR) and jaw-opening reflex (JOR) responses resulting from conditioning stimulation in the hypothalamus were studied in anesthetized rabbits. Stimulation of the lateral hypothalamus evoked a facilitation of the MMR and an inhibitory or facilitatory effect on the JOR. The facilitatory effect on JOR was stronger than that on the MMR. The facilitatory effective site for the JOR was in the dorsal and lateral directions as compared to the inhibitory field. The results suggest two functionally distinct regions in the lateral hypothalamus that separately project to the jaw-opening muscles.

Aggression↗

PubMed1986

Vestibulo-spinal response modification as determined with the H-reflex during the Spacelab-1 flight.

Our laboratory at the Johnson Space Center has employed the H-reflex recorded from the soleus muscle as a method of monosynaptic reflex testing in conjunction with vertical linear acceleration to assess modification of utriculo-saccular function induced through prolonged exposure to microgravity. It was hypothesized that exposure to free fall would reduce the necessity for postural reflexes in the major leg muscles, and that postural modification would reflect a change, not in the peripheral vestibular organs, but more centrally. This postural adjustment would reflect a sensory motor rearrangement where otolith receptor input was reinterpreted to provide an environmentally appropriate response. In addition to the H-reflex (which was the only inflight measurement), vestibulo-spinal EMG from the gastrocnemius, and self-motion reports were obtained in response to a sudden earth vertical fall. Preflight, inflight and postflight motion sickness reports were also recorded, and related to the H-reflex data. The results indicated that early inflight H-reflex amplitude was similar to that recorded preflight, but that measurements obtained later in the flight (day seven) did not show a change in potentiation as a function of the different drop to shock intervals. Immediate postflight H-reflex response in three of the four astronauts tested showed a rebound effect. Postflight gastrocnemius EMG in response to the sudden fall did not show a significant change from preflight values. However, one crewman who was tested early postflight did show an increase in EMG activity in response to the sudden fall. This immediate postflight effect returned to baseline rapidly. Self-motion perception obtained inflight suggested that the early inflight drops were perceived like those preflight. Drops later inflight were described as sudden, fast, hard and translational in nature. Immediately postflight the drops were perceived like those late inflight, and the astronauts said that they did not feel as though they were falling, rather the floor came up to meet them. Post hoc peak H-reflex amplitude, both preflight and postflight was related to inflight space motion sickness.

Humans↗

PubMed1993

The antiparkinsonian agent budipine is an N-methyl-D-aspartate antagonist.

Budipine (1-t-butyl-4,4-diphenylpiperidine) is a novel antiparkinsonian agent. Its clinical efficacy has been proven in double-blind placebo-controlled trials. The mechanism of action of budipine, however, is unknown. Budipine selectively increased the threshold of N-methyl-D-aspartate (NMDA)-induced seizures in mice. Similar to known specific NMDA antagonist, budipine depressed polysynaptic spinal reflexes in mice, but had no consistent effect on spinal monosynaptic reflexes. In receptor binding experiments, budipine displaced thienylcyclohexylpiperidyl-3,4-[3H]-(n) ([3H]-TCP) from its binding site with an IC50 of 36 microM suggesting that budopine acts as a non-competitive NMDA antagonist with moderate receptor affinity. It is concluded that the newly discovered NMDA antagonistic action of budipine is at least partly responsible for its antiparkinsonian activity. Our findings are additional evidence for the hypothesis that NMDA antagonists may be useful in the treatment of Parkinson's disease (PD).

Amino Acids↗

PubMed1989

Nerve section alters the interaction between C-fibre activity and intrathecal neuropeptides on the flexor reflex in rat.

The hamstring flexor reflex evoked by C-fibre strength electric shocks to the sural nerve was recorded in unanaesthetised, decerebrate, spinalized rats with sciatic nerves intact or sectioned 14-21 days previously. The effect of a brief C-fibre strength conditioning stimulus (CS) train (20 s, 1 Hz) to the sural nerve or intrathecally applied neuropeptides substance P (SP), vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) on reflex excitability were quantified. The sural CS and all of the neuropeptides caused a brief (1-5 min) facilitation of the test reflex with no concomitant changes in the amplitude of the monosynaptic reflex. A synergistic facilitatory interaction between the CS and SP, but not between the CS and VIP was observed in rats with intact nerves. In nerve-sectioned animals no synergism was found between CS and SP, but a very strong synergistic facilitation was seen with CS and VIP. Since SP and VIP both coexist with CGRP in separate populations of primary afferents, the interaction between SP plus CGRP and VIP plus CGRP was tested in animals with intact and sectioned nerves. In animals with intact nerves, SP and CGRP had a strong synergistic effect, whereas VIP and CGRP had a weak facilitatory interaction. In animals with sectioned nerves, SP and CGRP did not interact, whereas VIP and CGRP had a stronger facilitatory interaction. Since it has been shown that there are changes in peptide levels in primary afferents and dorsal horn interneurons following nerve section, it is proposed that such alterations may underly some of the physiological changes in spinal cord function after damage to peripheral nerves.

Animals↗

PubMed1980

The Hoffmann reflex of the soleus muscle. A study in leprosy.

The H reflex of the soleus muscle was used to investigate the monosynaptic reflex arc of two groups of leprosy patients compared with a similar group of normal subjects. The H reflex recordings show two abnormalities: (1) An increase in the latency of the reflex without difference between lepromatous and borderline patients. (2) A decrease of the Hmax:Mmax amplitude ratio more pronounced in the lepromatous group. The discrepancy between these results and the commonly described preservation of the deep tendon reflexes in leprosy is discussed and the hypothesis that leprosy neuropathy would affect all nerve trunks related to blood vessel changes in suggested.

Adolescent↗

PubMed1991

Limitedly selective action of a delta-agonistic leu-enkephalin on the transmission in spinal motor reflex pathways in cats.

1. The influence of the delta-opioid receptor agonist (D-Ser2)-leu-enkephalin (Thr6) (DSLET) on different spinal reflex pathways was investigated in anaemically decapitated, high spinal cats. Monosynaptic reflexes were tested to analyse excitatory and inhibitory flexor reflex afferent (FRA) pathways from nociceptive (from the skin of the central pad) and non-nociceptive (from skin, joint or group II muscle) afferents, as well as an excitatory nociceptive non-FRA pathway from the central pad to plantaris and intrinsic foot extensors and the inhibitory pathway from Ib muscle afferents. 2. DSLET suffused over the spinal cord (concentration 10(-3)-10(-6) M) caused a concentration-dependent depression of transmission in nociceptive and non-nociceptive FRA pathways. The excitatory FRA pathways including those from group II muscle afferents were more sensitive than the inhibitory ones. The nociceptive non-FRA pathway from the central pad to plantaris and intrinsic foot extensors was less affected than the FRA pathways. The inhibitory pathway from Ib muscle afferents remained almost unaffected. 3. Intravenous injection of DSLET (0.5-3.6 mg/kg) induced dose-dependent effects similar to those from local spinal application. The main difference was that I.V. injection more readily caused depression of the inhibitory FRA pathways to extensors. 4. The effects of local spinal application and of I.V. injection of DSLET were antagonized by I.V. injection of naloxone (0.1-1 mg/kg). 5. The effects of DSLET on spinal reflex pathways in many respects resemble that of monoamines. Possibly there is an interaction and a co-operation of enkephalins and monoamines in motor control.

Afferent Pathways↗

PubMed1984

LSD but not methysergide reduces the inhibitory effect of the medullary raphe stimulation on the spinal reflex in rats.

Conditioning stimulation of the nucleus raphe in the rat medulla enhanced the monosynaptic reflex (MSR) and depressed the polysynaptic reflex (PSR) in separate time courses. The PSR decreasing effect was reduced in preparations pretreated with reserpine, PCPA, or 5,6-DHT. The MSR increasing effect was not altered by these three pretreatments. Intravenously administered LSD but not methysergide reduced the PSR decreasing effect with no influence on the MSR increasing effect. These two drugs had similar effects on the unconditioned responses; the MSR was decreased and the PSR was increased. Thus, the PSR decreasing effect seems to be mediated via a serotonergic pathway probably descending from the nucleus raphe.

Animals↗

PubMed1985

Voluntary muscle release is not accompanied by H-reflex inhibition in patients with upper moto neuron lesions.

Changes in excitability of the soleus (Sol) monosynaptic reflex arc were investigated in spastic subjects, affected by amyotrophic lateral sclerosis (ALS), upon voluntary relaxation of tonic contraction of triceps surae muscle. Force and electromyograms (EMG) were recorded during triceps release, performed in response to an acoustic signal, in a reaction-time (RT) situation. Sol H-reflex was evoked at random during the task, and its amplitude was referred in time to the end of Sol EMG. At variance with the results for the same task in normal subjects, it was found that in ALS patients the RTs of the termination of EMG were longer than those of the beginning of the EMG, the decrease in force was prolonged and perturbed owing to intercurrent clonus-like EMG activity, and the H-reflex did not undergo the expected profound inhibition. It is suggested that the absence of the activation of presynaptic inhibitory mechanisms by the descending command to release brings about major disorders in voluntary muscle relaxation.

Amyotrophic Lateral Sclerosis↗

PubMed2000

Central control components of a 'simple' stretch reflex.

The monosynaptic stretch reflex is a fundamental feature of sensory-motor organization in most animal groups. In isolation, it serves largely as a negative feedback devoted to postural controls; however, when it is involved in diverse movements, it can be modified by central command circuits. In order to understand the implications of such modifications, a model system has been chosen that has been studied at many different levels: the crayfish walking system. Recent studies have revealed several levels of control and modulation (for example, at the levels of the sensory afferent and the output synapse from the sensory afferent, and via changes in the membrane properties of the postsynaptic neuron) that operate complex and highly adaptive sensory-motor processing. During a given motor task, such mechanisms reshape the sensory message completely, such that the stretch reflex becomes a part of the central motor command.

Animals↗

PubMed2003

Inhibition of spinal reflexes by acetylsalicylate and metamizol (dipyrone) in rats.

The effects of acetylsalicylate and metamizol on spinal monosynaptic reflexes were tested in spinal rats. Adult rats were anesthetized with ketamine, artificially ventilated, and spinalized at the C1 level. A laminectomy was performed in the lumbosacral region. Following electrical stimulation of the sciatic nerve by single pulses, the reflex potentials were recorded from the ipsilateral L5 ventral root. Acetylsalicylate was administered orally via nasogastric tube and metamizol intramuscularly. Acetylsalicylate (50 and 100 mg/kg) and metamizol (15 mg/kg) significantly decreased the amplitude of the reflex response (p < 0.05). But the 10-mg/kg metamizol dose did not significantly decrease the amplitude of the reflex response. The cyclooxygenase products of arachidonic acid may play an important role in regulating the reflex potential.

Animals↗

PubMedDate not supplied

[A change in the reflex excitability of spinal motoneurons during daytime sleep in newborn infants].

Studies have been made on monosynaptic reflexes elicited by the electrical stimulation of the ulnar and peroneal nerves (H-reflexes) in 5-7-day infants during sleep and in the awake state. During the orthodox stage of sleep, which is characterized by slow oscillations in EEG and by synchronous respiratory movements of the thorax and abdomen, the amplitude of H-refelexes was the highest, variation coefficient being the lowest. During paradoxical stage of sleep, characterized by desynchronized EEG, the presence of rapid movements of the eyes and by asynchronous respiratory movements of the thorax and abdomen, the amplitude of H-reflex comprised 25-40% of this parameter during the orthodox sleep, variation coefficient exceeding 100%. In the awake state, the amplitude of H-reflexes was equal to 60% of that during the orthodox sleep.

Humans↗

PubMedDate not supplied

Changes in reflex excitability of spinal motor neurons during day sleep in newborn infants.

A study was made of monosynaptic reflexes elicited by electrical stimulation of the ulnar and fibular nerves (H-reflexes) in newborn children, age five to seven days, during the sleeping--waking cycle. The amplitude of the H-responses was maximal and the coefficient of variation was minimal during the orthodox sleep state (OS) characterized by slow EEG waves and synchronous movement of the chest and stomach. During paradoxial sleep (PS), characterized by desynchronous EEG activity, rapid eye movements, and asynchronous breathing movements of the chest and stomach, the amplitude of the H-responses fell to 25 to 40% of the level during OS, and the coefficient of variation was in excess of 100%. The amplitude of H responses during the waking state was 60% that of the OS stage. The results of the study are considered from the point of view of existing theories about the reorganization of the system of controlling movements during the sleeping--waking cycle.

Humans↗

PubMed1990

Effects of ingested doses of caffeine on neuromuscular reflex response time in man.

To determine the effect of two doses of caffeine on a caudal (monosynaptic) reflex in humans, 30 subjects were randomly assigned to one of three groups. The groups received one of the following doses of caffeine per kilogram body weight using a double blind, placebo controlled design: 6 mg/kg, 3 mg/kg or a placebo. All of the subjects were similarly caffeine naive and were instructed to fast eight hours, refrain from caffeine for 96 hours, and avoid strenuous exercise 48 hours prior to testing. At the pre-test and post-test all subjects were given three trials of the patellar ligament reflex. Following pre-testing, subjects ingested either the caffeine solutions or an inert solution. After a one hour absorption period, subjects were post-tested. Gain scores were analyzed using a one-way ANOVA among the three groups, and a Newman-Keuls multiple range test was used to compare the three groups. The analysis revealed a significant difference in the gain score of the 6 mg/kg group. The control group had a mean gain of 4.3 msec, the 3 mg/kg group had a mean gain of 11.5 msec, and the 6 mg/kg group had a mean gain of 23.8 msec. Although the 6 mg/kg group was significantly different than the other two groups, a visible but nonsignificant difference was found between the 6 mg and 3 mg groups and the 3 mg and 0 mg groups. It was concluded that a 6 mg/kg dose of caffeine significantly lengthens reflex time in college age students.

Adult↗

PubMed1986

Periaqueductal gray inhibition of viscerointercostal and galvanic skin reflexes.

In adult cats anesthetized with urethan-chloralose, effects of descending volleys from the mesencephalic periaqueductal gray (PAG) upon the viscerointercostal and galvanic skin reflexes were studied. The viscerointercostal reflex (VIR) was evoked by electrical stimulation of the greater splanchnic nerve and was recorded from the 11th, 12th or 13th intercostal nerve. Conditioning stimuli applied to the PAG inhibited the VIR. The inhibition was particularly marked when the nucleus raphe dorsalis (NRD) or its immediately adjacent ventromedial PAG was stimulated. A train of pulses was required in order to produce a recognizable PAG/NRD inhibition of the VIR. When the PAG/NRD was stimulated at 300-500 Hz, stimulation-produced inhibition became more pronounced in parallel with increase in number of pulses in each train and levelled off at about 5 pulses. The most effective frequency of PAG/NRD stimulation was found within this frequency range. Degree of PAG/NRD stimulation-produced inhibition of the VIR was dependent upon the strength of the test stimulus applied to the splanchnic nerve; the weaker the test stimulus, the more marked the inhibition. PAG/NRD stimulation-produced inhibition of the VIR was completely eliminated by bilateral section of the dorsolateral funiculi. The same section enhanced the VIR per se. It was suggested that PAG/NRD stimulation-produced inhibition of the VIR is mediated by descending pathways in the ipsi- as well as contralateral dorsolateral funiculi, and that the VIR per se is tonically inhibited by descending impulses in these pathways. PAG/NRD stimulation inhibited the segmental polysynaptic reflex in the intercostal nerve, but had little effect on the segmental monosynaptic reflex in the same nerve. Intravenous administration of morphine suppressed the VIR. The suppression was antagonized by intravenous naloxone. In contrast, PAG/NRD stimulation-produced inhibition of the VIR was unaffected by intravenous naloxone. Electrical stimulation of the splanchnic nerve evoked the galvanic skin reflex (GSR) from the forepaw pad. The GSR was inhibited by electrical stimulation of the PAG/NRD. The PAG/NRD stimulation-produced inhibition of the GSR was completely eliminated by intravenous administration of naloxone (0.4 mg/kg).

Animals↗

PubMed1992

Altered patterns of reflex excitability subsequent to contusion injury of the rat spinal cord.

1. The present study investigated regulation of reflex excitability after experimental contusion injury of the spinal cord. 2. Four measures of H-reflex excitability were evaluated in normal rats and at 6, 28, and 60 days after contusion injury at the T8 level: 1) reflex thresholds, 2) slope of the reflex recruitment curves, 3) maximal plantar H-reflex/maximal plantar M-response (Hmax/Mmax) ratios, and 4) rate-sensitive depression (i.e., the decrease in reflex magnitude relative to repetition rate). 3. Tested as a function of the afferent volley magnitude, the thresholds for reflex initiation fell progressively subsequent to contusion injury. No change was observed at 6 days postinjury, and the decrease at 28 days was not significant. However, by 60 days postinjury, the threshold had decreased by 23% of the maximal afferent volley, and this decrease was significant, [analysis of variance (ANOVA, P < or = 0.01)]. 4. Hmax/Mmax ratios elicited in postcontusion animals at 0.3 Hz were not significantly different from those recorded in normal animals. 5. The slopes of the recruitment curves were markedly reduced subsequent to contusion injury. The decrease was greatest at 6 days postinjury. Although some recovery toward normal occurred at 28 and 60 days postinjury, the slopes of recruitment curves in postcontusion animals remained significantly decreased. 6. H-reflexes elicited at 1-5 Hz were less sensitive to rate depression in postcontusion animals than in normal animals at the same respective frequencies. The decrease was progressive in onset, becoming significant by 28 days postinjury, and of an enduring nature, i.e., still significantly different from normal in the reflexes tested 60 days postinjury. 7. Rate sensitivity of the tibial nerve monosynaptic reflex (MSR) was also compared in normal and postcontusion animals. Rate sensitivity of the tibial MSRs was significantly reduced at 28 and 60 days post-contusion, compared with normal animals. 8. These data indicate that significant changes in lumbar reflex excitability result from midthoracic contusion injury of the spinal cord. These changes include reflex threshold, slope of recruitment, and rate-sensitive depression. Although recruitment slope was most altered in the shortest postinjury interval tested, followed by some recovery, the other changes were progressive in onset and enduring in duration.

Animals↗