A comparison a amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics.

OBJECTIVE: To compare amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. DESIGN: A double-blind, crossover trial of treatment with amitriptyline, maprotiline, and placebo. Treatment was given in randomized order for periods of 4 weeks. Each period was separated by a 1-week washout. The final dose was 75 mg/day for both amitriptyline and maprotiline. PATIENTS: Thirty-seven patients with diabetic and nondiabetic painful polyneuropathy. OUTCOME MEASURES: The treatment effects were assessed by daily ratings of pain intensity on a 10-step verbal scale (0 = no pain and 10 = worst thinkable pain) and at the end of each treatment period by a global rating of the analgesic effect on a 5-step verbal scale (pain relief scale). For the assessment of depression, the Comprehensive Psychopathological Rating Scale (CPRS) was used. RESULTS: Using the global assessment of pain relief at the end of each treatment period, 22 of 33 patients reported reduced pain on amitriptyline treatment compared with 14 of 33 patients on maprotiline treatment and 8 patients on placebo treatment (p < .0001 and p < .05 for amitriptyline and maprotiline, respectively, against placebo). Amitriptyline was slightly better than maprotiline (p < .05) [tested by repeated measures analysis of variance (ANOVA)]. The order in which treatments occurred and the diagnosis of diabetes or nondiabetes did not have any significant effect on the global rating of pain relief. The mean values of the daily ratings of pain intensity showed that pain was more severe in the evenings than in the mornings and that diabetic patients reported worse pain than nondiabetics at baseline. The mean values of pain reduction as assessed with the 10-step verbal scale during the 4th week of treatment showed that amitriptyline and maprotiline were significantly better than placebo in relieving the pain (p < .0001 and p < .01, respectively, post hoc test according to Scheffé). However, there was no significant difference between the pain reduction of amitriptyline compared with maprotiline when assessing pain reduction with the 10-step verbal scale during the 4th treatment week. Nor was there a significant difference between diabetics and nondiabetics with regard to the effect of the drugs. The clinical effect was not significantly correlated to plasma concentration of either amitriptyline and its active metabolite nortriptyline or maprotiline in the global or daily assessments. The effect of treatment was not correlated to any particular pain quality nor to the intensity of pain. Depression was noted in three patients who completed the medication trial, but the effect of treatment of pain and depression did not clearly correlate. The adverse side effects of amitriptyline and maprotiline were common, and in 5 patients the medication had to be discontinued because of severe side effects. CONCLUSION: From the present results and the literature, it is concluded that tricyclic antidepressants with a pharmacologic profile similar to amitriptyline are the most effective drugs in the treatment of polyneuropathy pain in both diabetic and nondiabetic patients.

Laser-evoked cerebral potentials and sensory function in patients with central pain.

Central pain syndromes (CPS) could be caused by disinhibition of spinothalamic excitability or by other central nervous system (CNS) changes caused by reduced spinothalamic function. To examine these possibilities, we studied 11 patients (ages 51-82 years) with unilateral central pain and with reproducible cerebral evoked vertex potentials in response to cutaneous stimulation of the normal side with pulses from an infra-red CO2 laser. All patients had normal tactile and kinesthetic sensation; one had slightly decreased vibratory sense bilaterally. All showed, from the unaffected (asymptomatic) side, laser evoked potentials (LEPs) with negative (N) components ranging from 208 to 280 msec peak latency (av: 240 +/- 6 SE msec) and peak amplitudes of 1-7 microV (av: 2.9 +/- 0.5 SE microV), followed, in all but 1 patient, by positive (P) potentials ranging from 288 to 370 msec peak latency (av: 319 +/- 7.7 SE msec) with peak amplitudes of 1-7 microV (2.8 +/- 0.5 SE microV). Laser stimulation of the affected (symptomatic) side in 5 patients evoked LEPs with N-P interpeak amplitudes that were within 20% of those evoked from the normal side. All but one of these patients had thresholds for warm, heat pain, and deep pain that were normal in comparison with the unaffected side. The excepted patient had the largest N-P interpeak amplitude asymmetry (18.5%) of this group. Ratings of laser pulse intensity were either symmetrical (n = 2) or increased on the affected side (n = 3) in these patients. In contrast, laser stimulation of the affected side failed to evoke either N or P potentials in 6 patients, all of whom had lateralized increased thresholds for warm, heat pain, or deep pain, or reduced ratings of laser pulse sensation. Although 1 patient had increased ratings of laser pulse sensation, the amplitude of the LEP was always reduced on the side of increased pain or heat threshold in these CPS patients (Fisher exact test: P = 0.015). These results reflect primarily a deficit in spinothalamic tract function and do not suggest excessive CNS responses to synchronous activation of cutaneous heat nociceptors in patients with CPS.

[Subacute sensory neuropathies]. / Subakuta sensoriska neuropatier.

A 52 year old woman, previously healthy apart from a mild chronic persisting hepatitis, developed a sensory ataxia one week after an acute febrile illness. Clinically she had a severe impairment of proprioception and kinesthesia in the arms. Neurophysiological examinations demonstrated absent sensory potentials in the hands. No malignancy was found, and the patient had no sicca symptoms. Some tests for Sjögren's syndrome were positive, but not conclusive. A slight improvement followed after the acute phase. The diagnosis is compatible with an idiopathic subacute sensory neuronopathy.

Clinical, neurophysiological and immunological evidence of polyneuropathy in patients with monoclonal gammopathies.

In this study we estimated the prevalence of polyneuropathy (PN) in patients with monoclonal gammopathies. 31 patients with monoclonal gammopathies (19 with monoclonal gammopathy of uncertain significance (MGUS), 10 with multiple myeloma (MM), and 2 with Waldenström's macroglobulinemia), were studied by clinical and neurophysiological examination, blood tests to exclude other causes of PN, ELISA assays to detect antibodies to peripheral nerve myelin (PNM), and antibodies to myelin associated glycoprotein (MAG). 11 of 31 patients (36%) had a clinical PN, 3 (10%) had a probable PN (signs but no symptoms), and 4 (13%) had a subclinical PN (only neurophysiological signs of PN). Thus, in total 18 patients (58%) had some form of PN, in contrast to an age-matched control group (n = 33) where only 2 persons (6%) had some form of PN; 1 had a probable PN and 1 had a subclinical PN. 3 patients had anti-PNM and anti-MAG antibodies of IgM isotype, all 3 patients showing a demyelinating PN. The remaining patients with PN had a mild or moderate distal PN. One patient had a myelopathy and 1 had amyotrophic lateral sclerosis (ALS). IgM isotype of the M-protein was associated with a high risk of clinical PN (5 out of 6 (83%)), in contrast to IgG (5 out of 18 (28%)) and IgA (1 out of 6 (17%)). We conclude that PN is a common finding in patients with monoclonal gammopathies, but only some of them are of the demyelinating type and associated with antibodies to PNM or MAG.

Transcranial cortical stimulation. Late excitability changes in the soleus and anterior tibial motoneurone pools.

The effect of conditioning magnetic transcranial cortical stimulation (TCCS) on the excitability levels of the soleus and anterior tibial motoneurone pools was studied by Hmax/2 technique 40-400 msec after the stimulus. The target muscles were relaxed throughout the tests. Two periods of facilitation (the first at 80-100 msec and the second at 180-200 msec) were found. They shared approximately the same latencies as the late responses (S100 and S > 150) that we have previously recorded following TCCS. A period of inhibition that started at 150 msec was also recorded. A period of facilitation could also be noted when the conditioning stimulus was applied either over the deltoid muscle or when the click that accompanied the magnetic pulse was used. This suggests that brain-stem areas related to those of the startle reaction play an important role for the appearance of the facilitatory changes. The necessary input probably comes from both peripheral and cortical sources.

Effects of epidural bupivacaine or mepivacaine on somatosensory evoked potentials and skin resistance responses.

OBJECTIVE: The main purpose of this study was to compare the depth of neural block in lumbar epidural analgesia using either 20 mg/ml mepivacaine or 5 mg/ml bupivacaine. METHODS: Sixteen healthy patients were randomly divided to receive blindly either 17.5 ml mepivacaine (median, 15-20) or 17.5 ml bupivacaine (median, 14-20) for lumbar epidural analgesia. Afferent block was assessed by somatosensory evoked potentials (SEPs) during electrical stimulation of cutaneous sensory nerves at the T10, L1, L4, and L5 dermatomes. Efferent block was assessed by skin resistance responses (SRRs) recorded from the hand (C6), T12-L1, and foot (L5). RESULTS: Upper level of analgesia (pin-prick, cold) was T4 (T1-11) in the mepivacaine group and T4-5 (T2-9) in the bupivacaine group. In the mepivacaine group, SEPs were abolished in seven of eight cases at the T10 stimulation level and in five of eight cases at the L1 level. In the bupivacaine group, SEPs were abolished in two of eight cases at the T10 level and in three of eight cases at the L1 level. At the L4 and L5 levels, SEPs were only slightly changed in both groups. In the mepivacaine group, SRRs were completely or almost completely blocked (0-35% of control values) in all of eight cases at both the T12-L1 level and in the foot. Corresponding values for bupivacaine were six of seven and five of eight, respectively. Skin resistance responses in the foot and hand were significantly (p less than 0.05) lower in cases with abolished SEPs at the T10 stimulation level compared with those cases with preserved (although reduced) SEPs. CONCLUSIONS: Twenty mg/ml mepivacaine produces a more complete neural block than 5 mg/ml bupivacaine. The responsiveness of the afferent and efferent limbs of the nervous system was blocked in a similar manner as was shown by depression of the SEPs and SRRs.

Antibodies to peripheral nerve myelin may occur without clinical neuropathy in healthy persons.

To study the role of autoantibodies against peripheral nerve myelin (PNM), sera from 255 healthy blood donors were investigated by enzyme-linked immunosorbent assay (ELISA), and persons with anti-PNM antibodies were further studied clinically and by neurography, 25 blood donors (10%) had anti-PNM antibodies of IgM, IgG or IgA isotype. The 12 blood donors with anti-PNM antibodies of IgM isotype showed only slightly decreased nerve conduction velocities compared to 12 blood donors without anti-PNM antibodies. Two blood donors with anti-PNM antibodies of IgM and IgG isotype respectively showed a clinical, previously undiagnosed polyneuropathy (PN), verified by neurography. However, also one blood donor without anti-PNM antibodies had a clinical and neurography-verified PN. We conclude that antibodies against PNM may occur in healthy persons without evidence of a clinical or subclinical PN.

Correlation between dynamic posturography, clinical investigation, and neurography in patients with polyneuropathy.

Dynamic posturography (PG) is a new objective method to study functional performance in diseases affecting balance. It measures muscle response latencies and sway angles to standardized alterations of a moveable platform and moveable surroundings. Twenty-eight patients with polyneuropathy (PN) were studied by clinical investigation, vibrametry, neurography, and dynamic PG. The results of dynamic PG and vibrametry were compared with those of 29 healthy controls. In the patients with PN, clinical scores correlated to the latencies of the muscle response when the platform was suddenly moved forward, and to equilibrium performance (sway angles) in dynamic PG test conditions with eyes closed and the platform either stable or 'sway-referenced'. That is, the platform moves in response to the patient's anterior-posterior sway, creating a disturbed proprioceptive input to the brain. Clinical scores also correlated to the equilibrium performance when both platform and surroundings were sway-referenced. In conclusion dynamic PG, in addition to clinical investigations and neurophysiology, is a valuable and objective method for estimating the equilibrium performance in patients with PN.

Neuropathy and myopathy in primary Sjögren's syndrome: neurophysiological, immunological and muscle biopsy results.

Seventeen consecutive patients with primary Sjögren's syndrome (PSS) received neurophysiological examination, analysis of antibodies against peripheral nerve-myelin (PNM) and muscle biopsy, to show the prevalence and characteristics of peripheral neuropathy (PN) and myopathy; 3 PSS cases showed a clinical mild sensorimotor polyneuropathy, 1 of them had been treated with cytostatic drugs; 1 had mononeuropathia multiplex; and 1 clinical carpal tunnel syndrome. In these 5 patients neurophysiological investigation verified the clinical diagnosis of peripheral nerve involvement; 2 with PN had serum-antibodies against PNM; 1 of IgM-, and 1 of IgA-isotype. Muscle biopsies were taken from 15 PSS patients; 11 showed inflammatory myositis or inflammatory perivascular infiltrates and 3 showed signs of denervation. A combination of inflammation and morphological signs of myopathy, compatible with the biopsy diagnosis of polymyositis, was seen in 4, 1 of whom showed clinical signs of polymyositis. We conclude that the peripheral nervous and muscular systems are often involved in PSS, but commonly with relatively mild symptoms and laboratory findings. The common findings of inflammatory myopathy indicate an immune reaction in muscles in addition to other autoimmune manifestations of the disease.

Late muscular responses to transcranial cortical stimulation in man.

Transcranial cortical stimulation was performed in healthy human subjects. Electrical and magnetic stimuli were applied over the motor areas of the hand and the leg. Surface EMGs were recorded from the antagonistic extensor and flexor carpi radialis and the anterior tibial and triceps surae muscles. Except for the well known early (primary) responses several secondary responses have been recorded. (1) A response with a latency of approximately 100 msec and with higher threshold than the primary response. It was found in approximately half of the muscles recorded from except for the anterior tibial where it was comparatively rare. It could appear both contra- and ipsilaterally and increased in amplitude with preactivation of the target muscle. It is probably not of startle origin but its appearance may be influenced by an approximately simultaneous startle effect from the scalp stimulus. (2) In some subjects a response with a latency of 50-60 msec was recorded. Sometimes it was easily separated from the primary response and from S 100 but sometimes the differentiation was difficult. (3) It was found that the known inhibitory period which follows the primary response was contralateral and increased in duration with increasing stimulus strength. The increase in duration may be due to inhibitory feedback from receptors activated by the simultaneously increasing primary muscle twitch. (4) In relaxed muscle we also observed a contralateral response with a latency exceeding 150 msec. The latency increased with increasing stimulus strength. This increase seems to be related to discontinuance of the inhibitory period.

Central post-stroke pain--somatosensory evoked potentials in relation to location of the lesion and sensory signs.

Somatosensory evoked potentials (SEPs) were studied in 27 patients with central post-stroke pain and in 19 controls. A scoring system for SEP was used, in which increasing abnormalities rendered increasing scores. SEPs evoked by electrical stimulation of the median and tibial nerves were compared to perception thresholds for touch, vibration, innocuous and noxious temperature. All patients had reduced temperature sensibility, while the threshold for touch and vibration was abnormal in only 52% and 41%, respectively. Decreased touch and vibration sensibility had a high correlation with high SEP scores, while no correlation was found between reduced temperature sensibility and SEP. The patients with thalamic lesions had the most severely affected SEPs, the ones with lower brain-stem lesions were the least affected. The results support the notion that the SEP is dependent on the lemniscal pathways and that lesions of the spinothalamic pathways are crucial for the development of CPS.

Internal neurolysis or ligament division only in carpal tunnel syndrome. II. A 3 year follow-up with an evaluation of various neurophysiological parameters for diagnosis.

48 patients with clinical and neurophysiological signs of carpal tunnel syndrome were randomized to any of two operative methods: Internal neurolysis of the median nerve with a microsurgical technique, or simple division of the carpal ligament (flexor retinaculum). After a minimum follow-up period of 3 years 81% of the patients did not report any complaints at all, and all patients considered themselves improved after operation. There was no difference between the operation groups. Therefore there seems to be no justification to perform the more difficult procedure of internal microsurgical neurolysis for treatment of the carpal tunnel syndrome. A study of the neurophysiological parameters before and after restitution showed the highest sensitivity (91%) for the sensory conduction velocity, and the highest specificity for motor distal latency and sensory distal latency (83 and 75% resp.).