Normal Proprioceptive Trigeminal Merents in Patients with Sjogren’s Syndrome and Sensory Neuronopathy Josep Valls-Sole, MD,+ Francesc Graus, MD,“ Josep Font, MD,P Adolf Pou, MD,$ and Eduard S. Tolosa, MDL
A pure sensory neuropathy due to neuronal damage in the gasserian and spinal ganglia has been described inpatients with Sjogren’s syndrome. Conventional electromyographic (EMG) studies can demonstrate the selective involvement of the sensory pathways but they do not provide definite evidence for the site of the lesion. Noting that the trigeminal sensory neurons carrying cutaneous and muscular afferents are differentially located in the gasserian and mesencephalic nuclei, respectively, we carried out an electrophysiological study of the trigeminofacial and trigeminotrigemi n d reflexes in 5 patients with Sjogren’s syndrome and pure sensory neuropathy, in 10 patients withsensory-motor neuropathies of other causes, and in 10 healthy subjects. Our results show that patients with Sjogren’s syndrome and pure sensory neuropathy who exhibited abnormal blink reflexes and an abnormal, cutaneous-induced masseter silent period had normal jaw jerks, whereas patients with sensory-motor neuropathies who exhibited abnormal cutaneous responses had abnormal jaw jerks. These findings suggest that the lesion in pure sensory neuropathy involvesdamage to the neurons of the gasserian ganglia and not to the trigeminal axons, since an axonal lesion would be expected to involve the large axons from muscle spindle receptors. Valls-Sole J, Graus F, Font J, Pou A, Tolosa ES. Normal proprioceptive trigeminal afferents in patients with Sjogren’s syndrome and sensory neuronopathy. Ann Neurol 1990;28:786-790
A pure sensory neuropathy (PSN) has been described in patients with SjGgren’s syndrome (SS) 11, 2). In contrast to the classic sensory-motor neuropathy due to vascular lesions 13, 41, PSN is attributed to damage of neuronal bodies of the dorsal root and gasserian ganglia [l}.PSN is characterized by asymmetrical sensory involvement, usually starting in the upper limbs and affecting predominantly kinesthetic and vibratory sensations; abolition of deep tendon reflexes in all limbs; and frequent association with Adie’s pupil and trigeminal sensory involvement {l, 2, 5}. Although conventional electrophysiological tests demonstrate that the deficit is confined to the sensory system, they cannot prove that the lesion is in the cell body, even when both the peripheral and the central responses to sensory stimulation are absent { 5 , 61. In the trigeminal nerve, it is not possible to record the action potential of the peripheral sensory nerves and the technique for recording the evoked potentials is still not well developed [7, S}. In order to better characterize the site of impairment on the trigeminal nerve, we carried out an electrophysiological study of the trigeminofacial and trigeminotrigemind reflexes in patients with PSN. The same was performed in patients with other types of
From the *Neurology Service and tInternal Medicine Service, Hospital Clinic, and the :tInstitut of Neurology, Hospital del Mar. P. Maritim, Barcelona, Spain. Received Mar 19, 1990, and in revised form Jun 15. Accepted for publication Jun 18, 1990.
peripheral neuropathy in which the trigeminal nerve was involved clinically or electrophysiologically, or both. The results allowed us to distinguish patients with PSN from those with other neuropathies and suggest a primary impairment of gasserian ganglia neurons in the former.
Patients and Methods The study included 5 patients with PSN and primary SS, 10 patients with sensory-motor neuropathies, and 10 healthy subjects. The diagnosis of SS was made according to classic criteria [9}. Xerophthalmia was confirmed by a positive result on Schirmer’s test and characteristic rose bengal staining. Xerostomia was confirmed by abnormal scintigraphic findings in the salivary gland and a positive finding on examination of a minor salivary gland biopsy specimen. All patients were women. Their mean age was 44.4 years, ranging between 28 and 75 years. Clinical, immunological, and conventional electrophysiological aspects were reported elsewhere [5, 61. In short, sensory symptoms (mainly vibratory and position sense loss) predominated in the hands. Muscle strength was normal and tendon reflexes were universally absent. Adie’s pupil was observed in 3 patients. Trigeminal sensory involvement was present in 2 patients. Anti-Ro antibodies were Address correspondence to Dr Valls-Sole, Unitat d‘EMG, Servei de Neurologia, Hospital Clinic, Villarroel, 170. 08036, Barcelona, Espaiia.
786 Copyright Q 1990 by the American Neurological Association
found in 4 patients. No patient showed the presence of specific antibodies against neural antigens [lo}. Needle electromyographic (EMG) findings, motor nerve conductions, and F-wave studies were normal. H-reflexes and T waves were absent in all muscles of the four limbs. Action potentials of the sensory nerves were either absent, abnormally small, or normal, depending on the nerve examined { S ] . Corresponding absence or abnormal results were found in the somesthetic evoked potentials. All patients with sensory-motor neuropathies exhibited clinical and/or electrophysiological evidence of trigeminal nerve involvement. Based on electrophysiological criteria from a conventional examination, 5 of these patients had predominantly demyelinating polyneuropathies (1 patient each had chronic Guillain-Barr6 syndrome, osteosclerotic myeloma with monoclonal gammopathy, and severe diabetic polyneuropathy; 2 patients had the hypertrophic form of Charcot-Marie-Toothdisease). The remaining 5 patients had multifocal axonal neuropathies (2 patients had antibodies to human immunodeficiency virus (HIV), 2 patients were diabetic, and l patient had Lyme disease). Ten subjects with no known neurological disease were used as controls. All patients and control subjects were examined by the same person in the same room, with approximately the same temperature and environment. All electrophysiological studies were performed using a two-channel electromyograph MEDELEC MS8 (MEDELEC Limited, Old Woking, Surrey, England) and standard techniques and electrodes [Ill. Needle EMG was performed in the masseter muscle of both sides. The compound muscle action potential (CMAP)of the facial nerve to supramaxirnal electrical stimulation was recorded by using a pair of cutaneous electrodes placed on the orbicularis oculi muscle. Blink reflexes were obtained using the same recording electrodes by applying electrical stimuli to the ipsilateral and contralateral supraorbital nerve and also to the infraorbital nerve. T response of the masseter muscle, or jaw jerk, was recorded through a cutaneous electrode over the muscle belly with reference to the earlobe. The stimuli were mechanical taps applied to the chin with an oscilloscope triggering hammer (MEDELEC 11290) while the mouth was kept slightly open. Reflex silent periods (SP) or suppression of the masseter EMG activity were obtained during a sustained voluntary contraction of the masseter muscles by applying a tap to the chin (mechanical SP) or an electrical stimulus to the mental nerve (cutaneous SP). Presence or absence of responses and their latencies were evaluated in each test. Negative peak amplitude was measured in the CMAP of the facial nerve and in the masseteric T wave. Duration of the SP was measured by superimposition of at least three sweeps. Abnormal SPs were considered when EMG activity suppression was either absent or severely reduced in all recordings. Semiquantitativemeasurements (+, + +, and +) of denervation signs were made at rest with needle EMG recording of the masseter muscle. Both sides of the face were examined in each subject. Pooled data for each measurement were compared statistically between groups of subjects using Student’s t test.
oculi response to infraorbital or mental nerve stimulation and the masseteric T response evoked by mandibular tap (jaw jerk) were found within the normal range reported in the literature El2-151. Chin taps elicited a period of EMG activity suppression or SP in both masseter muscles, with an abrupt onset and end. Electrical stimulation of the mental nerve evoked a SP in both masseter muscles that showed two phases: an early one, with a duration similar to that of the SP obtained by chin taps, and a later one, that came after a period of breakthrough EMG activity [l5]. In patients with SS and PSN, findings on facial nerve tests and masseter EMG recordings were normal. Blink-reflex responses were delayed or absent in most instances. Only the responses obtained in one side of the face in 1 patient were within normal limits. In most patients, there was absence of blink-reflex responses to infraorbitary or mental nerve stimulation. The latency and amplitude of masseter T response were normal in all patients (9 > 0.05), compared with control subjects. Mechanical stimulation to the chin evoked an SP with normal duration, but electrical stimulation to the mental nerve gave rise to an abnormal masseteric SP, which was absent in 2 patients and greatly reduced with indistinct onset and end in the other 3. Such abnormalities were more evident in the later phase of the response. In patients with demyelinating diseases, delayed responses were found in all tests. Occasional responses were absent or unrecognizable. The mean amplitude of the facial CMAP was significantly reduced when compared with control subjects (p < 0.05) and its shape was always polyphasic. The onset of the masseter T response was greatly delayed. The masseter SP to mechanical or electrical stimuli was usually present but significantly delayed in all patients @ < 0.05). Its duration was slightly increased. In patients with axonal neuropathies, some responses were absent. When they were present, the onset latency was normal or only moderately delayed. There was EMG evidence of denervation in all 5 patients. The mean amplitude of the facial CMAP was significantly reduced when compared with control subjects @ < 0.05). The masseter T response was absent in one side of the face in 4 patients. In the fifth patient, a noticeable latency and amplitude asymmetry was observed between sides. O n mechanical as well as electrical stimulation, the masseter SP was absent or severely reduced in most patients. Characteristic masseter T responses are shown in Figure 1 and electrically elicited masseter SPs, in Figure 2.
Results
Discussion By the criteria of Schaumburg and Spencer {lb], the PSN of patients with SS is a neuronopathy. This is
++
The results of all tests are summarized in the Table. In the control group, the blink reflex and the obicularis
Valls-Sole et al: Trigeminal Nerve in Sensory Neuronopathy 787
Results of Trigemznofacial TestJa
Testb
CG (20)
Masseter EMG (denervation signs) Facial CMAP
SM-A (10)
+
0
01
3.2 2.1
3.1 2.2
8.2' 0.9'
0
0
0
11.1
14.6' 40.4 45.7
18.5' 50.5 50.8 1
14.5' 41.3 42.4 3
48.8 3
44. I 3
35.6 36.1 0
5
O/+l+
41.6
0
6
6.9 0.8
6.7 0.9 0
11.4' 0.3' 1
4
10.5 22.7 0
10.9 20.1 0
20.5' 27' 3
13.1' 19.3 6
11.2 23.9 43.4 43.8 0
12.8 17.3' 46.6 37.2 8
18.3' 28.1 59.5' 43.0 5
13.2 21.1 45.4 52.0 7
0
+
3.8 0.9' 1
36.3
Latency
Amplitude Abnormal responses Mechanical SP Latency Duration Abnormal responses Cutaneous SP1 latency Duration SP2 latency Duration Abnormal responses
SM-D (10)
0
Latency
Amplitude Abnormal responses Blink reflex R1 latency R2 latency R2c latency Abnormal responses Infraorbitary R2 latency Abnormal responses Jaw reflex
PSN (10)
7.5' 0.5'
"Numher of examinations are given in parentheses. Numbers represent the mean value among all measured responses and are given in milliseconds (latency and duration) and millivolts (amplitude). hAbnormal responses are absent or severely reduced, nonmeasurable responses. ' p < 0.05 when compared to control group. CG = control group of healthy subjects; PSN = patients with Sjogren's syndrome and pure sensory neuropathy; SM-D demyelinating neuropathies; SM-A = patients with axonal neuropathies; CMAP = compound muscle action potential.
strongly supported by the histological finding of lymphocyte infiltrates in dorsal root ganglion [I] and the absence of vasculitis in peripheral nerve biopsy specimens [2, 171. To OUT knowledge, there is no report on biopsy studies of the trigeminal nerve in patients with SS and PSN. Findings on supraorbital nerve biopsy have been reported by Lecky and colleagues [18] in a patient with trigeminal sensory ncuropathy of unknown cause, in whom the severe loss of large myelinated fibers without vascular inflammatory changes suggested damage of the gasserian ganglia neurons. The main findings of our study are the documentation of subclinical involvement of the trigeminal nerve and the observation of a normal jaw jerk in patients with SS and PSN. Only 2 patients complained of facial sensory loss, but the results of electrophysiological tests, either the blink reflex or the electrically elicited masseter SP, were abnormal in all. The patients with sensory-motor neuropathies also Complained of loss of facial sensation and the blink reflex and masseter SP were also abnormal. By contrast, the jaw jerk, which
788 Annals of Neurology Vol 28
=
patients with
tests the function of masseter spindle afferents, was normal in patients with PSN but abnormal in patients with sensory-motor neuropathies. Thus, a normal masseter reflex with an abnormal blink reflex may differentiate PSN from other neuropathies involving the trigeminal nerve. It is worth monitoring tendon reflexes, especially of the masseter muscle, which is often difficult to assess by inspection [13, 191. Our results in the study of masseter SPs agree with the findings in jaw reflex. Patients with PSN exhibited normal stretch-induced SPs and abnormal electrically induced SPs, whereas patients with sensory-motor neuropathies exhibited abnormal results in both SPs. The suppression of masseter EMG activity following a tap to the chin is due to activation of inhibitory afferents and to the withdrawal of excitation of the muscle spindle receptors [14]. When the SP is evoked through electrical stimulation of the mental nerve, however, muscle spindle receptors are not likely to be activated and the EMG activity suppression is probably due solely to the inhibitory cutaneous afferents.
No 6 December 1990
A
A
I
‘i
‘*
D
C
~
Fig 1. Masseter &ex (T wave). Upper traces: right side; lower traces: l4t side. (A)Patient with Sjogren’r syndrome and pure sensory neumpathy. (Bj Patient with demyelinating neuropathy. (Cj Patient with axonal neuropathy with lejit trigemznal nerve involvement.
From our results, it appears that patients with SS and PSN have a dysfunction of trigeminal skin receptors whereas the function of trigeminal stretch receptors is spared. These findings are explained by the fact that trigeminal neurons that carry the peripheral inputs from masseter spindle afferents are located within the central nervous system in the mesencephalic nucleus [20), whereas the cutaneous sensory neurons lie in the gasserian ganglion. Thus, our findings are compatible with a lesion selectively affecting the neurons of the gasserian ganglia. If the lesion were axonal, one would not expect the muscle spindle afferents to be spared. Patients with either axonal or demyelinating peripheral neuropathies show the impairment of both the cutaneous and the muscular trigeminal afferents. This distinction may help to differentiate axonopathies from neuronopathies in the trigeminal nerve. Patients with SS and PSN have absent T waves or tendon reflexes in the upper or lower limbs [ S , 61. This also suggests damage in the dorsal root ganglia neurons carrying inputs from spindle receptors of the limb muscles. Although the autoimmune mechanisms underlying SS originate outside the nervous system, they could damage neurons of the dorsal root and gasserian ganglia due to the partial absence of a bloodbrain barrier [2 11. The preservation of trigeminal proprioceptive neurons, the only muscle spindle afferents
Fig 2. Masseter EMG activity suppression (SP) to electrical stimuli. Upper tracci: right masseter muscle; lmuer traces: lejit masseter muscle. (A) Subject with no neurological diseaJe. (B) Patient with Sjogren’s syndrome and pure sensory neuropathy. (C) Patient with demyelinating neuropathy. (0)Patient with axonal neuropathy involving the trigeminal nerve. S = stimulus to the lefi mental nerve.
protected by the blood-brain barrier, suggests that the autoimmune response does not reach the central nervous system. We conclude that abnormal blink reflex and cutaneous-induced SPs together with normal jaw jerk and stretch-induced SPs are characteristic signs of the lesion of the gasserian ganglia neurons in patients with SS and PSN.
Addendum While this article was in press, the extensive study by Griffin and colleagues appeared E22). These authors studied 13 patients with Sjogren’s syndrome who, like the patients of our study, had a predominantly ataxic sensory neuropathy. Their findings provide further evidence of dorsal root ganglionitis with lymphocytic T-cell infiltration as the underlying pathology in this type of neuropathy. References 1. Malinow K, Yannakakis GD, Glusman SM, et al. Subacute sensory neuronopathy secondary to dorsal root ganglionitis in primary Sjogren’s syndrome. Ann Neurol 1986;20:535-537 2. Graus F, Pou A, Kanterewicz E, Anderson NE. Sensory neuronopathy and Sjogren’s syndrome: clinical and immunological study of two patients. Neurology 1988;38:1637-1639 3. Kennet RP, Harding AE. Peripheral neuropathy associated with
Valls-Sole et al: Trigeminal Nerve in Sensory Neuronopathy
789
the sicca syndrome. J Neurol Neurosurg Psychiatry 1986;49: 90-92 4. Alexander EL, Provost TT, Stevens MB, Alexander GE. Neurologic complications of primary Sjogren’s syndrome. Medicine 1982;61:247-25 7 5. Font J, Valls J, Cervera R, et al. Pure sensory neuropathy in patients with primary Sjogren’s syndrome: clinical, immunological and electromyographic findings. Ann Rheum Dis (in press) 6. Valls-Sole J, Graus F. Electrophysiologic study of patients with pure sensory neuropathy. Electroencephalogr Clin Neurophysiol 1990;75(1):Sl55 7. Cruccu G, Bowsher D. Intracranial stimulation of the trigeminal nerve in man. 11. Reflex responses. J Neurol Neurosurg Psychiatry 1986;49:419-427 8. Leandri M, Parodi CI, Favale E. Early evoked potentials detected from the scalp of man following infraorbital nerve stimulation. Electroencephalogr Clin Neurophysiol 1985;62:99-107 9. Morrow J, Isenberg D. Sjogren’s syndrome. In: MorrowJ, Isenberg D (eds). Autoimmune rheumatic disease. Oxford: Blackwell Scientific, 1987:208-233 10. Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear anbibody in sensory neuronopathy from lung cancer. Neurology 1985;35:538-543 11. Kimura J. Electrodiagnosis in diseases of the nerve and muscle: principles and practice. Philadelphia: F.A. Davis, 1983:83-104 12. Kimura J, Rodnitzky RL, van Allen WM. Electrodiagnostic study of the trigeminal nerve. Orbicularis oculi reflex and masseter reflex in trigeminal neuralgia, paratrigeminal syndrome and other lesions of the trigeminal nerve. Neurology 1970; 201574-583
790 Annals of Neurology
3. Ongerboer de Visser BV, Goor C. Electromyographic and reflex study in idiopathic and symptomatic trigeminal neuralgias: latency of the jaw and blink reflexes. J Neurol Neurosurg Psychiatry 1974;37:1225-1230 4. Lund JP, Lamarre Y, Lavigne G, Duquet G. Human jaw reflexes. Adv Neurol 1983;39:739-755 15. Ongerboer de Visser BW, Goor C. Cutaneous silent period in masseter muscles: a clinical and electrodiagnostic evaluation. J Neurol Neurosurg Psychiatry 1976;39:674-679 16. Schaumburg H H , Spencer PS. Toxic neuropathies. Neurology 1979;29:429-431 17. Hankey GJ, Gubbay SS. Peripheral neuropathy associated with sicca syndrome. J Neurol Neurosurg Psychlatry 1987;50: 1085 18. Lecky BRF, Hughes RAC, Murray NMF. Trigeminal sensory neuropathy. A study of 22 cases. Brain 1987;110:1463-1485 19. Ongerboer de Visser BW, Goor C . Jaw reflexes and masseter electromyograms in mesencephalic and pontine lesions: an electrodiagnostic study. J Neurol Neurosurg Psychiatry 1976;39: 90-92 20. Ongerboer de Visser BW. Anatomical and functional organitation of reflexes involving the trigeminal system in man: jaw reflex, blink-reflex, corneal reflex and exteroceptive suppression. In: Desmedr JE, ed. Motor control mechanisms in health and disease. New York Raven Press, 1983:727-738 2 1. Jacobs JM, MacFarlane RM, Cavanagh JB. Vascular leakage in the dorsal root ganglia of the rat studied with horseradish peroxidase. J Neurol Sci 1976;29:95-107 22. Griffin JW, Cornblath DR, Alexander E, et al. Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjogren’s syndrome. Ann Neurol 1990;27:304-3 15
Vol 28 No 6 December 1990
A pure sensory neuropathy due to neuronal damage in the gasserian and spinal ganglia has been described inpatients with Sjogren’s syndrome. Conventional electromyographic (EMG) studies can demonstrate the selective involvement of the sensory pathways but they do not provide definite evidence for the site of the lesion. Noting that the trigeminal sensory neurons carrying cutaneous and muscular afferents are differentially located in the gasserian and mesencephalic nuclei, respectively, we carried out an electrophysiological study of the trigeminofacial and trigeminotrigemi n d reflexes in 5 patients with Sjogren’s syndrome and pure sensory neuropathy, in 10 patients withsensory-motor neuropathies of other causes, and in 10 healthy subjects. Our results show that patients with Sjogren’s syndrome and pure sensory neuropathy who exhibited abnormal blink reflexes and an abnormal, cutaneous-induced masseter silent period had normal jaw jerks, whereas patients with sensory-motor neuropathies who exhibited abnormal cutaneous responses had abnormal jaw jerks. These findings suggest that the lesion in pure sensory neuropathy involvesdamage to the neurons of the gasserian ganglia and not to the trigeminal axons, since an axonal lesion would be expected to involve the large axons from muscle spindle receptors. Valls-Sole J, Graus F, Font J, Pou A, Tolosa ES. Normal proprioceptive trigeminal afferents in patients with Sjogren’s syndrome and sensory neuronopathy. Ann Neurol 1990;28:786-790
A pure sensory neuropathy (PSN) has been described in patients with SjGgren’s syndrome (SS) 11, 2). In contrast to the classic sensory-motor neuropathy due to vascular lesions 13, 41, PSN is attributed to damage of neuronal bodies of the dorsal root and gasserian ganglia [l}.PSN is characterized by asymmetrical sensory involvement, usually starting in the upper limbs and affecting predominantly kinesthetic and vibratory sensations; abolition of deep tendon reflexes in all limbs; and frequent association with Adie’s pupil and trigeminal sensory involvement {l, 2, 5}. Although conventional electrophysiological tests demonstrate that the deficit is confined to the sensory system, they cannot prove that the lesion is in the cell body, even when both the peripheral and the central responses to sensory stimulation are absent { 5 , 61. In the trigeminal nerve, it is not possible to record the action potential of the peripheral sensory nerves and the technique for recording the evoked potentials is still not well developed [7, S}. In order to better characterize the site of impairment on the trigeminal nerve, we carried out an electrophysiological study of the trigeminofacial and trigeminotrigemind reflexes in patients with PSN. The same was performed in patients with other types of
From the *Neurology Service and tInternal Medicine Service, Hospital Clinic, and the :tInstitut of Neurology, Hospital del Mar. P. Maritim, Barcelona, Spain. Received Mar 19, 1990, and in revised form Jun 15. Accepted for publication Jun 18, 1990.
peripheral neuropathy in which the trigeminal nerve was involved clinically or electrophysiologically, or both. The results allowed us to distinguish patients with PSN from those with other neuropathies and suggest a primary impairment of gasserian ganglia neurons in the former.
Patients and Methods The study included 5 patients with PSN and primary SS, 10 patients with sensory-motor neuropathies, and 10 healthy subjects. The diagnosis of SS was made according to classic criteria [9}. Xerophthalmia was confirmed by a positive result on Schirmer’s test and characteristic rose bengal staining. Xerostomia was confirmed by abnormal scintigraphic findings in the salivary gland and a positive finding on examination of a minor salivary gland biopsy specimen. All patients were women. Their mean age was 44.4 years, ranging between 28 and 75 years. Clinical, immunological, and conventional electrophysiological aspects were reported elsewhere [5, 61. In short, sensory symptoms (mainly vibratory and position sense loss) predominated in the hands. Muscle strength was normal and tendon reflexes were universally absent. Adie’s pupil was observed in 3 patients. Trigeminal sensory involvement was present in 2 patients. Anti-Ro antibodies were Address correspondence to Dr Valls-Sole, Unitat d‘EMG, Servei de Neurologia, Hospital Clinic, Villarroel, 170. 08036, Barcelona, Espaiia.
786 Copyright Q 1990 by the American Neurological Association
found in 4 patients. No patient showed the presence of specific antibodies against neural antigens [lo}. Needle electromyographic (EMG) findings, motor nerve conductions, and F-wave studies were normal. H-reflexes and T waves were absent in all muscles of the four limbs. Action potentials of the sensory nerves were either absent, abnormally small, or normal, depending on the nerve examined { S ] . Corresponding absence or abnormal results were found in the somesthetic evoked potentials. All patients with sensory-motor neuropathies exhibited clinical and/or electrophysiological evidence of trigeminal nerve involvement. Based on electrophysiological criteria from a conventional examination, 5 of these patients had predominantly demyelinating polyneuropathies (1 patient each had chronic Guillain-Barr6 syndrome, osteosclerotic myeloma with monoclonal gammopathy, and severe diabetic polyneuropathy; 2 patients had the hypertrophic form of Charcot-Marie-Toothdisease). The remaining 5 patients had multifocal axonal neuropathies (2 patients had antibodies to human immunodeficiency virus (HIV), 2 patients were diabetic, and l patient had Lyme disease). Ten subjects with no known neurological disease were used as controls. All patients and control subjects were examined by the same person in the same room, with approximately the same temperature and environment. All electrophysiological studies were performed using a two-channel electromyograph MEDELEC MS8 (MEDELEC Limited, Old Woking, Surrey, England) and standard techniques and electrodes [Ill. Needle EMG was performed in the masseter muscle of both sides. The compound muscle action potential (CMAP)of the facial nerve to supramaxirnal electrical stimulation was recorded by using a pair of cutaneous electrodes placed on the orbicularis oculi muscle. Blink reflexes were obtained using the same recording electrodes by applying electrical stimuli to the ipsilateral and contralateral supraorbital nerve and also to the infraorbital nerve. T response of the masseter muscle, or jaw jerk, was recorded through a cutaneous electrode over the muscle belly with reference to the earlobe. The stimuli were mechanical taps applied to the chin with an oscilloscope triggering hammer (MEDELEC 11290) while the mouth was kept slightly open. Reflex silent periods (SP) or suppression of the masseter EMG activity were obtained during a sustained voluntary contraction of the masseter muscles by applying a tap to the chin (mechanical SP) or an electrical stimulus to the mental nerve (cutaneous SP). Presence or absence of responses and their latencies were evaluated in each test. Negative peak amplitude was measured in the CMAP of the facial nerve and in the masseteric T wave. Duration of the SP was measured by superimposition of at least three sweeps. Abnormal SPs were considered when EMG activity suppression was either absent or severely reduced in all recordings. Semiquantitativemeasurements (+, + +, and +) of denervation signs were made at rest with needle EMG recording of the masseter muscle. Both sides of the face were examined in each subject. Pooled data for each measurement were compared statistically between groups of subjects using Student’s t test.
oculi response to infraorbital or mental nerve stimulation and the masseteric T response evoked by mandibular tap (jaw jerk) were found within the normal range reported in the literature El2-151. Chin taps elicited a period of EMG activity suppression or SP in both masseter muscles, with an abrupt onset and end. Electrical stimulation of the mental nerve evoked a SP in both masseter muscles that showed two phases: an early one, with a duration similar to that of the SP obtained by chin taps, and a later one, that came after a period of breakthrough EMG activity [l5]. In patients with SS and PSN, findings on facial nerve tests and masseter EMG recordings were normal. Blink-reflex responses were delayed or absent in most instances. Only the responses obtained in one side of the face in 1 patient were within normal limits. In most patients, there was absence of blink-reflex responses to infraorbitary or mental nerve stimulation. The latency and amplitude of masseter T response were normal in all patients (9 > 0.05), compared with control subjects. Mechanical stimulation to the chin evoked an SP with normal duration, but electrical stimulation to the mental nerve gave rise to an abnormal masseteric SP, which was absent in 2 patients and greatly reduced with indistinct onset and end in the other 3. Such abnormalities were more evident in the later phase of the response. In patients with demyelinating diseases, delayed responses were found in all tests. Occasional responses were absent or unrecognizable. The mean amplitude of the facial CMAP was significantly reduced when compared with control subjects (p < 0.05) and its shape was always polyphasic. The onset of the masseter T response was greatly delayed. The masseter SP to mechanical or electrical stimuli was usually present but significantly delayed in all patients @ < 0.05). Its duration was slightly increased. In patients with axonal neuropathies, some responses were absent. When they were present, the onset latency was normal or only moderately delayed. There was EMG evidence of denervation in all 5 patients. The mean amplitude of the facial CMAP was significantly reduced when compared with control subjects @ < 0.05). The masseter T response was absent in one side of the face in 4 patients. In the fifth patient, a noticeable latency and amplitude asymmetry was observed between sides. O n mechanical as well as electrical stimulation, the masseter SP was absent or severely reduced in most patients. Characteristic masseter T responses are shown in Figure 1 and electrically elicited masseter SPs, in Figure 2.
Results
Discussion By the criteria of Schaumburg and Spencer {lb], the PSN of patients with SS is a neuronopathy. This is
++
The results of all tests are summarized in the Table. In the control group, the blink reflex and the obicularis
Valls-Sole et al: Trigeminal Nerve in Sensory Neuronopathy 787
Results of Trigemznofacial TestJa
Testb
CG (20)
Masseter EMG (denervation signs) Facial CMAP
SM-A (10)
+
0
01
3.2 2.1
3.1 2.2
8.2' 0.9'
0
0
0
11.1
14.6' 40.4 45.7
18.5' 50.5 50.8 1
14.5' 41.3 42.4 3
48.8 3
44. I 3
35.6 36.1 0
5
O/+l+
41.6
0
6
6.9 0.8
6.7 0.9 0
11.4' 0.3' 1
4
10.5 22.7 0
10.9 20.1 0
20.5' 27' 3
13.1' 19.3 6
11.2 23.9 43.4 43.8 0
12.8 17.3' 46.6 37.2 8
18.3' 28.1 59.5' 43.0 5
13.2 21.1 45.4 52.0 7
0
+
3.8 0.9' 1
36.3
Latency
Amplitude Abnormal responses Mechanical SP Latency Duration Abnormal responses Cutaneous SP1 latency Duration SP2 latency Duration Abnormal responses
SM-D (10)
0
Latency
Amplitude Abnormal responses Blink reflex R1 latency R2 latency R2c latency Abnormal responses Infraorbitary R2 latency Abnormal responses Jaw reflex
PSN (10)
7.5' 0.5'
"Numher of examinations are given in parentheses. Numbers represent the mean value among all measured responses and are given in milliseconds (latency and duration) and millivolts (amplitude). hAbnormal responses are absent or severely reduced, nonmeasurable responses. ' p < 0.05 when compared to control group. CG = control group of healthy subjects; PSN = patients with Sjogren's syndrome and pure sensory neuropathy; SM-D demyelinating neuropathies; SM-A = patients with axonal neuropathies; CMAP = compound muscle action potential.
strongly supported by the histological finding of lymphocyte infiltrates in dorsal root ganglion [I] and the absence of vasculitis in peripheral nerve biopsy specimens [2, 171. To OUT knowledge, there is no report on biopsy studies of the trigeminal nerve in patients with SS and PSN. Findings on supraorbital nerve biopsy have been reported by Lecky and colleagues [18] in a patient with trigeminal sensory ncuropathy of unknown cause, in whom the severe loss of large myelinated fibers without vascular inflammatory changes suggested damage of the gasserian ganglia neurons. The main findings of our study are the documentation of subclinical involvement of the trigeminal nerve and the observation of a normal jaw jerk in patients with SS and PSN. Only 2 patients complained of facial sensory loss, but the results of electrophysiological tests, either the blink reflex or the electrically elicited masseter SP, were abnormal in all. The patients with sensory-motor neuropathies also Complained of loss of facial sensation and the blink reflex and masseter SP were also abnormal. By contrast, the jaw jerk, which
788 Annals of Neurology Vol 28
=
patients with
tests the function of masseter spindle afferents, was normal in patients with PSN but abnormal in patients with sensory-motor neuropathies. Thus, a normal masseter reflex with an abnormal blink reflex may differentiate PSN from other neuropathies involving the trigeminal nerve. It is worth monitoring tendon reflexes, especially of the masseter muscle, which is often difficult to assess by inspection [13, 191. Our results in the study of masseter SPs agree with the findings in jaw reflex. Patients with PSN exhibited normal stretch-induced SPs and abnormal electrically induced SPs, whereas patients with sensory-motor neuropathies exhibited abnormal results in both SPs. The suppression of masseter EMG activity following a tap to the chin is due to activation of inhibitory afferents and to the withdrawal of excitation of the muscle spindle receptors [14]. When the SP is evoked through electrical stimulation of the mental nerve, however, muscle spindle receptors are not likely to be activated and the EMG activity suppression is probably due solely to the inhibitory cutaneous afferents.
No 6 December 1990
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Fig 1. Masseter &ex (T wave). Upper traces: right side; lower traces: l4t side. (A)Patient with Sjogren’r syndrome and pure sensory neumpathy. (Bj Patient with demyelinating neuropathy. (Cj Patient with axonal neuropathy with lejit trigemznal nerve involvement.
From our results, it appears that patients with SS and PSN have a dysfunction of trigeminal skin receptors whereas the function of trigeminal stretch receptors is spared. These findings are explained by the fact that trigeminal neurons that carry the peripheral inputs from masseter spindle afferents are located within the central nervous system in the mesencephalic nucleus [20), whereas the cutaneous sensory neurons lie in the gasserian ganglion. Thus, our findings are compatible with a lesion selectively affecting the neurons of the gasserian ganglia. If the lesion were axonal, one would not expect the muscle spindle afferents to be spared. Patients with either axonal or demyelinating peripheral neuropathies show the impairment of both the cutaneous and the muscular trigeminal afferents. This distinction may help to differentiate axonopathies from neuronopathies in the trigeminal nerve. Patients with SS and PSN have absent T waves or tendon reflexes in the upper or lower limbs [ S , 61. This also suggests damage in the dorsal root ganglia neurons carrying inputs from spindle receptors of the limb muscles. Although the autoimmune mechanisms underlying SS originate outside the nervous system, they could damage neurons of the dorsal root and gasserian ganglia due to the partial absence of a bloodbrain barrier [2 11. The preservation of trigeminal proprioceptive neurons, the only muscle spindle afferents
Fig 2. Masseter EMG activity suppression (SP) to electrical stimuli. Upper tracci: right masseter muscle; lmuer traces: lejit masseter muscle. (A) Subject with no neurological diseaJe. (B) Patient with Sjogren’s syndrome and pure sensory neuropathy. (C) Patient with demyelinating neuropathy. (0)Patient with axonal neuropathy involving the trigeminal nerve. S = stimulus to the lefi mental nerve.
protected by the blood-brain barrier, suggests that the autoimmune response does not reach the central nervous system. We conclude that abnormal blink reflex and cutaneous-induced SPs together with normal jaw jerk and stretch-induced SPs are characteristic signs of the lesion of the gasserian ganglia neurons in patients with SS and PSN.
Addendum While this article was in press, the extensive study by Griffin and colleagues appeared E22). These authors studied 13 patients with Sjogren’s syndrome who, like the patients of our study, had a predominantly ataxic sensory neuropathy. Their findings provide further evidence of dorsal root ganglionitis with lymphocytic T-cell infiltration as the underlying pathology in this type of neuropathy. References 1. Malinow K, Yannakakis GD, Glusman SM, et al. Subacute sensory neuronopathy secondary to dorsal root ganglionitis in primary Sjogren’s syndrome. Ann Neurol 1986;20:535-537 2. Graus F, Pou A, Kanterewicz E, Anderson NE. Sensory neuronopathy and Sjogren’s syndrome: clinical and immunological study of two patients. Neurology 1988;38:1637-1639 3. Kennet RP, Harding AE. Peripheral neuropathy associated with
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the sicca syndrome. J Neurol Neurosurg Psychiatry 1986;49: 90-92 4. Alexander EL, Provost TT, Stevens MB, Alexander GE. Neurologic complications of primary Sjogren’s syndrome. Medicine 1982;61:247-25 7 5. Font J, Valls J, Cervera R, et al. Pure sensory neuropathy in patients with primary Sjogren’s syndrome: clinical, immunological and electromyographic findings. Ann Rheum Dis (in press) 6. Valls-Sole J, Graus F. Electrophysiologic study of patients with pure sensory neuropathy. Electroencephalogr Clin Neurophysiol 1990;75(1):Sl55 7. Cruccu G, Bowsher D. Intracranial stimulation of the trigeminal nerve in man. 11. Reflex responses. J Neurol Neurosurg Psychiatry 1986;49:419-427 8. Leandri M, Parodi CI, Favale E. Early evoked potentials detected from the scalp of man following infraorbital nerve stimulation. Electroencephalogr Clin Neurophysiol 1985;62:99-107 9. Morrow J, Isenberg D. Sjogren’s syndrome. In: MorrowJ, Isenberg D (eds). Autoimmune rheumatic disease. Oxford: Blackwell Scientific, 1987:208-233 10. Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear anbibody in sensory neuronopathy from lung cancer. Neurology 1985;35:538-543 11. Kimura J. Electrodiagnosis in diseases of the nerve and muscle: principles and practice. Philadelphia: F.A. Davis, 1983:83-104 12. Kimura J, Rodnitzky RL, van Allen WM. Electrodiagnostic study of the trigeminal nerve. Orbicularis oculi reflex and masseter reflex in trigeminal neuralgia, paratrigeminal syndrome and other lesions of the trigeminal nerve. Neurology 1970; 201574-583
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3. Ongerboer de Visser BV, Goor C. Electromyographic and reflex study in idiopathic and symptomatic trigeminal neuralgias: latency of the jaw and blink reflexes. J Neurol Neurosurg Psychiatry 1974;37:1225-1230 4. Lund JP, Lamarre Y, Lavigne G, Duquet G. Human jaw reflexes. Adv Neurol 1983;39:739-755 15. Ongerboer de Visser BW, Goor C. Cutaneous silent period in masseter muscles: a clinical and electrodiagnostic evaluation. J Neurol Neurosurg Psychiatry 1976;39:674-679 16. Schaumburg H H , Spencer PS. Toxic neuropathies. Neurology 1979;29:429-431 17. Hankey GJ, Gubbay SS. Peripheral neuropathy associated with sicca syndrome. J Neurol Neurosurg Psychlatry 1987;50: 1085 18. Lecky BRF, Hughes RAC, Murray NMF. Trigeminal sensory neuropathy. A study of 22 cases. Brain 1987;110:1463-1485 19. Ongerboer de Visser BW, Goor C . Jaw reflexes and masseter electromyograms in mesencephalic and pontine lesions: an electrodiagnostic study. J Neurol Neurosurg Psychiatry 1976;39: 90-92 20. Ongerboer de Visser BW. Anatomical and functional organitation of reflexes involving the trigeminal system in man: jaw reflex, blink-reflex, corneal reflex and exteroceptive suppression. In: Desmedr JE, ed. Motor control mechanisms in health and disease. New York Raven Press, 1983:727-738 2 1. Jacobs JM, MacFarlane RM, Cavanagh JB. Vascular leakage in the dorsal root ganglia of the rat studied with horseradish peroxidase. J Neurol Sci 1976;29:95-107 22. Griffin JW, Cornblath DR, Alexander E, et al. Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjogren’s syndrome. Ann Neurol 1990;27:304-3 15
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