Role of the masseter reflex in the assessment of subacute sensory neuropathy

In 3 patients with a severe pure sensory neuropathy of subacute onset, the masseter reflex remained normal despite absent blink reflex responses and absent stretch reflexes in the extremities. In 20 patients with primary disorders of peripheral nerve axons or myelin, the masseter reflex was abnormal. This study suggests that a normal masseter reflex in patients presenting with a pure sensory neuropathy favors a polyganglionopathy rather than a primary axonal sensory neuropathy, particularly if the blink reflex is abnormal. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:800–801, 1998.     

Jaw reflexes and masseter electromyograms in mesencephalic and pontine lesions: an electrodiagnostic study.

Jaw reflexes and masseter electromyograms were studied in five patients with mesencephalic and 11 patients with pontine lesions, vascular or tumorous in nature. In the former group jaw reflexes were abnormal, being delayed or absent, whereas masseter electromyograms were normal. In the latter group, both jaw reflexes and masseter EMG, showing denervation, were abnormal in six and both normal in five cases. It is suggested that the afferent limb of the human jaw reflex passes through the mesencephalic trigeminal nucleus. The methods proved to be valuable in the diagnosis of mesencephalic and pontine lesions involving the fifth cranial nerve.     

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.     

Hemimasticatory spasm: clinical and electrophysiologic observations.

Hemimasticatory spasm is a rare disorder of the trigeminal nerve that produces involuntary jaw closure due to paroxysmal unilateral contraction of jaw-closing muscles. We report three patients with this disorder. Electrophysiologic studies demonstrated normal blink and masseter reflexes. The masseter inhibitory reflex was absent during periods of spasm. Needle electromyography demonstrated irregular bursts of motor unit potentials that were identical to the pattern observed in hemifacial spasm. The electrophysiologic findings suggest ectopic excitation of the trigeminal motor root or its nucleus, an abnormality that is analogous to ectopic excitation of the facial nerve in hemifacial spasm. One patient improved temporarily with surgery, one improved while on treatment with carbamazepine, and another responded favorably to botulinum toxin injection.     

Crossed and uncrossed central effects of muscle spindle afferents from the lateral pterygoid muscle of the guinea pig

Physiological evidence is presented for the presence of stretch reflexes in the lateral pterygoid (Pt) muscle of the guinea pig. The central reflex effects of excitation of Pt stretch reflex afferents were also investigated. Passive lateral jaw displacement, which resulted in stretch of the Pt muscle on the side of jaw movement and stretch of the zygomatico-mandibularis (Z) muscle on the side contralateral to the movement, evoked increased EMG activity in these muscles. Stimulation of the trigeminal mesencephalic nucleus (mes V) evoked monosynaptic reflexes in both the Pt and Z nerves. Tonic stretch of the Pt muscle facilitated the monosynaptic reflex in the Pt nerve evoked by stimulation of mes V. Tonic vibration of the Pt muscle facilitated the mes V evoked monosynaptic reflex in the nerves to the ipsilateral Pt and contralateral Z muscles. Conversely, tonic vibration of the Z muscle facilitated the monosynaptic reflex evolved by mes V stimulation in the contralateral Pt and ipsilateral Z nerve. The results support the view that muscle spindles exist in the Pt and Z muscles and that there is a monosynaptic stretch reflex for both the Pt and Z muscles with cell bodies located in the mes V nucleus. It was also shown that the ipsilateral Pt muscle and the contralateral Z muscle act as synergists in the production of lateral jaw movements and that the organization of the stretch reflexes originating from the Pt and Z muscles support their synergistic action.     

Topodiagnostic value of brain stem reflexes

The masseter and medial pterygoid stretch reflexes, the masseter inhibitory reflexes, and the blink reflexes are useful diagnostic tools for evaluation of brain stem disorders. The structures mediating these reflexes are largely known. Characteristic changes of the normal response patterns due to various lesions have been described. Distinct reflex abnormalities indicate lesions at specific sites. Multireflex testing improves the accuracy with which localization can be made. A number of lesions suspected on clinical data may be confirmed by reflex findings only and not by imaging studies. Reflex testing can be utilized to demonstrate multiple lesions evoked by a single vascular event and evaluate dissemination of central nervous involvement in multiple sclerosis patients. © 1994 John & Sons, Inc.     

Focal conduction block in the dorsal root ganglion in experimental allergic neuritis.

Acute experimental allergic neuritis was induced in Lewis rats by inoculation with bovine intradural root myelin and adjuvants. In terminal experiments, sensory conduction was assessed in rats with hindlimb ataxia and weakness by stimulating the exposed sciatic nerve and recording directly from the exposed L-4 spinal nerve, dorsal root ganglion, dorsal root, and dorsal root entry zone. Focal conduction block was present in a high proportion of large-diameter fibers in the dorsal root ganglion. In contrast, nerve conduction in the peripheral nerve and spinal nerve was essentially normal apart from probable conduction block in some fibers in the proximal spinal nerve in a minority of rats. The afferent volley arriving at the dorsal root entry zone of the spinal cord was greatly reduced, as a consequence of the conduction block in the dorsal root ganglion and probable conduction block in the dorsal root. The M wave recorded from the fourth dorsal interosseus muscle of the hindfoot was normal in amplitude but slightly prolonged in latency and the H reflex was absent. These electrophysiological findings correlated well with the histological findings of inflammation and prominent demyelination in the dorsal root ganglia and dorsal roots with minimal involvement of the proximal spinal nerve and no involvement of the sciatic nerve. It is concluded that the hindlimb ataxia in rats with this form of acute experimental allergic neuritis is due to demyelination-induced nerve conduction block in the dorsal root ganglia and probably in the dorsal roots.     

Illusive transience of parvalbumin expression duringembryonic development of the primate spinal cord

Parvalbumin has been located by pre-embedding light- and electron microscopic immunohistochemical techniques in the spinal cords of monkey fetuses (Macaca fasciculata), ranging from E70 to E 123, and in young (P20) and young adult (3 years) Macaque monkeys. During the time window investigated, the main developmental events of parvalbumin-containing neural elements are that parvalbumin-positive dorsal root collaterals establish intercellular networks first around nerve cells of Clarke's nucleus, then in the motoneuron pool and finally in the upper dorsal horn. In each of these areas, location of the parvalbumin-positive network is gradually shifted from medial to lateral. Whenever an intercellular network is established, nerve cells innervated by parvalbumin-positive terminals of dorsal root collaterals start to express parvalbumin. Immunoreactivity of dorsal root axons is transient; it disappears first from the intercellular networks and, afterwards, also from the dorsal columns. However, the pericellular synaptic terminals and their post-synaptic nerve cells express parvalbumin into adulthood. It is concluded that some of the large (Type A) dorsal root ganglion cells are the first ones in the spinal reflex pathway to express parvalbumin, which is elicited and gradually increased in nerve cells synaptically innervated by parvalbumin-positive axon terminals. This seems to represent a specific case of activation (or desinhibiton) of the genome. Apparent "transience" of parvalbumin is due to the specific geometry of primary sensory neurons equipped with extremely long axonal processes, and the consequent specialities of axonal transport characteristics.     

Supraspinal regulation of spinal reflex discharge into cardiac sympathetic nerves

(1) In chloralose anaesthetized cats, reflex responses were recorded in inferior cardiac nerves following stimulation of intercostal nerves and hind limb afferent nerves. (2) In 80% of cats, a long latency reflex response alone was recorded, whereas, in the others, a short and long latency response was present to intercostal nerve stimulation. (3) In cats displaying only a long latency somatocardiac reflex response, damage to the ventral quadrant of the ipsilateral cervical spinal cord, through which runs a bulbospinal inhibitory pathway, resulted in the appearance of shorter latency reflexes to intercostal nerve stimulation. Lesions elsewhere in the cervical cord did not do this. (4) The characteristics of the early responses indicated that they were somatosympathetic reflexes and not dorsal root reflexes. (5) The early reflexes remained and the late reflex disappeared on subsequent complete transection of the spinal cord. The early reflexes were therefore spinal reflexes, and suppressed in the animal with cord intact. (6) Lesions at C4, which included a contralateral hemisection and a section of dorsal columns extending into the dorsal part of the lateral funiculus, abolished the inhibition of a sympathetic reflex that followed stimulation of some somatic afferent nerve fibres. These sections did not release the spinal reflex. Therefore, this reflex inhibition was not responsible for the suppression of the spinal somatosympathetic reflex. (7) The descending inhibitory influence on the segmental reflex pathway was not antagonized by strychnine, bicuculline or picrotoxin. (8) The possibility is discussed that the spinal reflex pathway into cardiac sympathetic nerves is tonically inhibited by a bulbospinal pathway originating from the classical depressor region of the ventromedial reticular formation.     

Jaw and blind reflexes in trigeminal nerve lesions. An electrodiagnostic study.

Eighteen patients with intracranial trigeminal nerve lesions were investigated electrodiagnostically. The trigeminal motor root function was studied on the basis of the jaw reflex and masseter myograms and was disturbed in all cases. The jaw reflexes were abnormal in 16 and the masseter myograms in eight cases. An impressive trigeminal sensory root function was obtained from blink reflex, which was abnormal in 12 cases. The results show the diagnostic value of bilateral recording of the jaw reflex in such patients.     

Ensheathing glia transplants promote dorsal root regeneration and spinal reflex restitution after multiple lumbar rhizotomy

Previously, we have shown that transplants of olfactory bulb ensheathing cells promoted regeneration of transected dorsal roots into the spinal cord. In this study, we assessed the ability of regenerating axons to make functional connections in the cord. Dorsal roots L3 to L6 were sectioned close to their entrance into the spinal cord and reapposed after injecting a suspension of ensheathing cells into each dorsal root entry zone (Group G). Afferent regeneration into the cord and recovery of spinal reflexes were compared with animals that received no injection (Group S) or culture medium without cells (Group C). Electrophysiological tests, to measure nerve conduction and spinal reflexes (H response and withdrawal reflex) evoked by stimulation of afferents of the sciatic nerve, were performed. At 14 days after surgery, H response was found in only 1 of 7 rats of Group G, and withdrawal reflexes were absent from all animals. At 60 days, the H response reappeared in 7 of 10 rats of Group G, and 1 of 5 of each of Groups C and S. The withdrawal reflex recovered in 4 of 10 rats of Group G, but in none of Groups C and S. Immunohistochemical labeling for CALCITONIN GENE– RELATED PEPTIDE (CGRP) in rats of Group G showed immunoreactive fibers entering the dorsal horn from sectioned roots, although at lower density than in the contralateral side. In conclusion, transplanted ensheathing cells promoted central regeneration and functional reconnection of regenerating sensory afferents. Ann Neurol 1999;45:207–215     

Subacute sensory neuropathy associated with carcinoma--an autopsy case report and an analysis of Japanese cases

A 68-year-old man was admitted to our hospital because of numbness in the hands and feet, and unsteady gait in August, 1986. On neurological examination, deep tendon reflexes were absent in all limbs without pathological reflexes. Superficial and deep sensory disturbances of a glove and stocking type up to the level of the elbow and the knee were observed. Pseudoathetosis was noted in the hands. His gait was ataxic and Romberg sign was positive. Muscle strength was slightly decreased. Sural nerve biopsy showed severe loss of large myelinated fibers. Laboratory studies for malignancy showed lung cancer (Squamous cell carcinoma). Left pneumonectomy was performed in November, 1986, but he died in March, 1987. At autopsy, neither metastasis nor direct infiltration of malignant cells in the central and peripheral nervous systems were present macroscopically and histopathologically. Degeneration of the dorsal root ganglion and the posterior columns of the spinal cord were remarkable. Since 1955, only 9 cases of subacute sensory neuropathy had been reported in Japan. We analysed 10 Japanese cases (including our case) to clarify the clinicopathological features of subacute sensory neuropathy. Clinically, ataxic gait, paresthesia, deep sensory disturbance, and depression of deep tendon reflexes were present in the majority of the cases. Neuropathologically, neuronal cell loss and degeneration of the dorsal root ganglion, posterior roots and posterior columns of the spinal cord were universal findings.     

Apoptosis of spinal interneurons induced by sciatic nerve axotomy in the neonatal rat is counteracted by nerve growth factor and ciliary neurotrophic factor

We have previously shown that not only motoneurons and dorsal root ganglion cells but also small neurons, presumably interneurons in the spinal cord, may undergo apoptotic cell death as a result of neonatal peripheral nerve transection in the rat. With the aid of electron microscopy, we have here demonstrated that apoptosis in the spinal cord is confined to neurons and does not involve glial cells at the survival time studied (24 hours). To define the relative importance of the loss of a potential target (motoneuron) and a potential afferent input (dorsal root ganglion cell) for the induction of apoptosis in interneurons in this situation, we have compared the distributions and time courses for TUNEL labeling, which detects apoptotic cell nuclei, in the L5 segment of the spinal cord and the L5 dorsal root ganglion after sciatic nerve transection in the neonatal (P2) rat. In additional experiments, we studied the effects on TUNEL labeling of interneurons after treatment of the cut sciatic nerve with either ciliary neurotrophic factor (CNTF) to rescue motoneurons or nerve growth factor (NGF) to rescue dorsal root ganglion cells. The time courses of the TUNEL labeling in motoneurons and interneurons induced by the lesion show great similarities (peak at 8-48 hours postoperatively), whereas the labeling in dorsal root ganglion cells occurs later (24-72 hours). Both CNTF and NGF decrease the number of TUNEL-labeled interneurons, but there is a regional difference, in that CNTF preferentially saves interneurons in deep dorsal and ventral parts of the spinal cord, whereas the rescuing effects of NGF are seen mainly in the superficial dorsal horn. The results are interpreted as signs of a trophic dependence on both the target and the afferent input for the survival of interneurons neonatally.     

Trigeminal sensory neuropathy associated with decreased oral sensation and impairment of the masseter inhibitory reflex

We describe 4 patients with severe trigeminal sensory neuropathy whose main disability resulted from impaired intraoral sensation associated with disturbances of mastication and swallowing. Each patient had an abnormal blink reflex and jaw jerk. In addition, the masseter inhibitory reflex was absent in 3 patients and abnormal in the 4th. This reflex plays a role in the reflex control of mastication and can easily be elicited in normal subjects by stimulation of the skin and mucous membrane in the distribution of the 2nd and 3rd divisions of the trigeminal nerve while the jaw-closing muscles are contracting. Disturbed intraoral sensation combined with impaired trigeminal reflexes (particularly the masseter inhibitory reflex) interferes with neural mechanisms that regulate chewing and can be a source of severe disability in patients with trigeminal sensory neuropathy.     

Effect of experimental posterior temporalis muscle pain on human brainstem reflexes.

OBJECTIVE: To study the modulation of jaw-stretch and blink reflexes by experimental posterior temporalis muscle pain. METHODS: Thirty healthy volunteers (15 males, 25.5+/-0.6 years and 15 females, 27.4 +/- 1.2 years) were included. Short-latency stretch reflex responses were evoked in the masseter and temporalis muscles by fast stretches (1 mm displacement, 10 ms ramp time) and the blink reflexes were evoked by painful electrical pulses (0.5 ms duration), delivered by a concentric electrode placed on the left lower forehead close to the supraorbital foramen before, during and 15 min after a period with experimentally induced muscle pain. RESULTS: The normalized peak-to-peak amplitude of the stretch reflex in the painful temporalis was significantly higher during pain in both males and females compared with pre- and post-pain conditions (P < 0.004). The R2 root mean square (RMS) of the blink reflex decreased significantly during muscle pain as compared to the pre-pain (P < 0.03) in both males and females. CONCLUSIONS: The present results indicated that experimental posterior temporalis muscle pain facilitates the jaw-stretch reflex, whereas the nociceptive specific blink reflex is inhibited. SIGNIFICANCE: Present study suggested that these reflexes are suitable models for probing pontine and medullary pain processing.     

Cutaneous silent period in masseter muscles: a clinical and electrodiagnostic evaluation.

In 35 normal subjects electromyographic silent periods were constantly evoked bilaterally in the masseter muscles during maximal contraction after unilateral electrical stimulation over the infraorbital or mental nerve. Findings in this study and data obtained in 30 patients suffering from trigeminal (26) and facial (four) nerve lesions suggest that the silent period evoked according to our methods is cutaneous in origin. The trigeminal sensory root forms the afferent limb of the silent period reflex. Its central pathway is thought to pass both crossed and uncrossed through the pons. Determination of the cutaneous silent period might be of value for the demonstration of trigeminal nerve lesions and to supplement results concerning other brain-stem reflexes.     

Nerve growth factor modulates the activation status and fast axonal transport of ERK 1/2 in adult nociceptive neurones

Mature dorsal root ganglion cells respond to neurotrophins, and the intracellular signalling pathways activated by neurotrophins have been characterized in vitro. We have now used immunocytochemistry and Western blots to examine the expression and activation of extracellular signal-regulated protein kinase-1/2 (ERK) in rat dorsal root ganglion cells in vivo, using antisera to total (tERK) and phosphorylated (pERK) forms. This has revealed a number of novel findings. tERK immunoreactivity is present in most dorsal root ganglion cells but is expressed most strongly in small (nociceptive) cells and, surprisingly, is absent in a population of large cells that expressed trkB or trkC but mainly lack p75(NTR) immunoreactivity. In contrast pERK is prominent in a few trkA cells and in satellite glial cells, and is further increased by NGF treatment. tERK and pERK both undergo fast anterograde and retrograde axonal transport, indicated by accumulation at a sciatic nerve ligature, and NGF reduces the level of retrograde pERK transport.     

Inflammation near the nerve cell body enhances axonal regeneration

Although crushed axons in a dorsal spinal root normally regenerate more slowly than peripheral axons, their regeneration can be accelerated by a conditioning lesion to the corresponding peripheral nerve. These and other observations indicate that injury to peripheral sensory axons triggers changes in their nerve cell bodies that contribute to axonal regeneration. To investigate mechanisms of activating nerve cell bodies, an inflammatory reaction was provoked in rat dorsal root ganglia (DRG) through injection of Corynebacterium parvum. This inflammation enhanced regeneration in the associated dorsal root, increasing 4-fold the number of regenerating fibers 17 d after crushing; peripheral nerve regeneration was not accelerated. A milder stimulation of dorsal root regeneration was detected after direct injection of isogenous macrophages into the ganglion. It is concluded that changes favorable to axonal regeneration can be induced by products of inflammatory cells acting in the vicinity of the nerve cell body. Satellite glial cells and other unidentified cells in lumbar DRG were shown by thymidine radioautography to proliferate after sciatic nerve transection or injection of C. parvum into the ganglia. Intrathecal infusion of mitomycin C suppressed axotomy-induced mitosis of satellite glial cells but did not impede axonal regeneration in the dorsal root or the peripheral nerve. Nevertheless, the similarity in reactions of satellite glial cells during 2 processes that activate neurons adds indirect support to the idea that non-neuronal cells in the DRG might influence regenerative responses of primary sensory neurons.     

Branching of sensory axons in the peripheral nerve of the rat

The currently accepted concept of a primary sensory cell is a cell that gives rise to a central process which passes through the dorsal root to the spinal cord and a peripheral process which passes to the periphery via a peripheral nerve. If this is correct, then there should be equal numbers of sensory axons in the dorsal root, dorsal root ganglion cells, and sensory axons in the proximal peripheral nerve. The present study obtains these counts in animals in which extraneous axons have been removed from the peripheral nerve and root. The counts indicate that there are approximately 2.3 sensory axons in the dorsal root and proximal peripheral nerve for each ganglion cell in the sacral segments of the rat. We interpret these data as indicating that there is significant branching of sensory axons in the dorsal root and proximal peripheral nerve and thus the generally accepted picture of a dorsal root ganglion cell is not correct for some, perhaps all, of these cells. We offer the speculation that this peripheral branching may be an indication of single sensory neurons having receptive fields in two separate locations, and thus this may be an anatomical explanation for certain types of referred pain.     

Restitution of function and collateral sprouting in the cat spinal cord: the partially hemisected animal

The hypothesis that collateral sprouting might be correlated with recovery of function was tested by a combination of behavioral and anatomical studies. Partial hemisections, sparing the dorsal columns, were made between T₁₂ and L₁ of cat spinal cord. Initially, all reflex and locomotor hindlimb activity was depressed ipsilaterally. During two postoperative weeks behavioral and electromyographic responses increased in response to intrinsic reflex elicitation but not to descending or crossed reflex elicitation. Marked improvement in use of the limb occurred as intrinsic reflex activity increased and became, in some cases, hyperactive. The status then remained stable for ten months. Since intrinsic reflexes are mediated by ipsilateral dorsal roots, the intraspinal distribution of L₅ or L₆ dorsal roots was determined by degeneration methods ten months after hemisection or by quantitative radioautography 20 days after hemisection. By both methods, the dorsal root distribution was found to be asymmetrical in the spinal gray. It was greater on the experimental side and the distribution was altered, having a greater distribution medially in Rexed's lamina VI and laterally in lamina VII. These anatomical changes are considered as signs of collateral sprouting from dorsal roots in response to degeneration of descending tracts on the same side. Dorsal root distribution to dorsal horn (laminae I–IV), motor nuclei, and nucleus gracilis is symmetrical. Regions of increased and of expanded dorsal root input can be correlated with electrophysiologically determined location of interneurons in the path of cutaneous reflexes and of stretch reflex facilitation. Behavioral and anatomical changes were selective; intrinsic reflexes recovered or became hyperactive and ipsilateral dorsal roots showed evidence of collateral sprouting during the recovery period, although a causal relationship between the two cannot be proven, by the present experiments.