Sensory integration in writer's cramp: comparison with controls and evaluation of botulinum toxin effect.

OBJECTIVE: Abnormal temporal and spatial sensory integration have been described in mixed groups of dystonic patients. We tested somatosensory integration and the effect of botulinum toxin (BoNT) in patients with writer's cramp (WC). METHODS: Median and ulnar SEPs were recorded in 29 WC patients and in 10 controls. We performed: individual and simultaneous stimulation of median and ulnar nerves (MU) and paired stimulation of median nerve at interstimulus-interval (ISI) of 40 and 100 ms. All the trials were repeated after blinded randomized treatment with placebo or BoNT-A. RESULTS: We found no differences between patients and controls in standard SEPs. Spatial (except for N9) and temporal suppression after ISI 40 were present in both groups for all the waves; after ISI 100, suppression was present only for N70. There were no differences between patients and controls. After BoNT-A treatment, no changes were observed. CONCLUSIONS: In contrast with previous findings in heterogeneous dystonic groups, and although some studies suggest impairment of spatial and temporal sensory discrimination in patients with focal dystonia, in our large cohort of patients with WC we found no evidence of abnormal somatosensory integration investigated by means of SEPs and no changes in somatosensory variables after BoNT-A treatment. SIGNIFICANCE: Our findings may suggest pathophysiological differences between focal and generalized dystonia, and may also point to an inferior sensitivity of SEPs in detecting abnormalities in sensory discrimination as compared to methods based on subjective discrimination.

Phenotype of Charcot-Marie-Tooth disease Type 2.

OBJECTIVE: To investigate the clinical and electrophysiologic phenotype of Charcot-Marie-Tooth disease (CMT) Type 2 in a large number of affected families. METHODS: We excluded CMT Type 1, hereditary neuropathy with liability to pressure palsies, and CMT due to Cx32 gene mutations by DNA analysis. We performed genetic analysis of the presently known CMT Type 2 genes. RESULTS: Sixty-one persons from 18 families were affected. Ninety percent of patients were able to walk with or without the help of aids. Proximal leg muscle weakness was present in 13%. Asymmetrical features were present in 15%. Normal or brisk knee reflexes were present in 36%. Extensor plantar responses without associated spasticity occurred in 10 patients from eight families. Only three causative mutations were identified in the MFN2, BSCL2, and RAB7 genes. No mutations were found in the NEFL, HSPB1, HSPB8, GARS, DNM2, and GDAP1 genes. CONCLUSIONS: At group level, the clinical phenotype of Charcot-Marie-Tooth disease (CMT) Type 2 is uniform, with symmetric, distal weakness, atrophy and sensory disturbances, more pronounced in the legs than in the arms, notwithstanding the genetic heterogeneity. Brisk reflexes, extensor plantar responses, and asymmetrical muscle involvement can be considered part of the CMT Type 2 phenotype. The causative gene mutation was found in only 17% of the families we studied.

Botulinum toxin for writer's cramp: a randomised, placebo-controlled trial and 1-year follow-up.

BACKGROUND: Botulinum toxin type A (BoNT-A) has become the treatment of choice for most types of focal dystonia. OBJECTIVE: To investigate the efficacy of BoNT-A injections in patients with writer's cramp in a double-blind, randomised, placebo-controlled trial and to evaluate the follow-up results. METHODS: Forty participants were randomised to treatment with either BoNT-A or placebo injections in two sessions. Trial duration was 12 weeks. The primary outcome measure was the patients' choice to continue with the treatment, despite its possible disadvantages. Secondary outcome measures included several clinical rating scales on the levels of impairment and disability. Assessments were made at baseline and 2 months (secondary outcomes) and 3 months (primary outcome). Duration of follow-up was 1 year. RESULTS: 39 patients completed the trial. Fourteen of 20 patients (70%) receiving BoNT-A reported a beneficial effect and chose to continue treatment, versus 6 of 19 patients (31.6%) in the placebo group (p = 0.03). The changes on most of the clinical rating scales were significantly in favour of BoNT-A. Side effects reported were hand weakness, which was mostly mild and always transient, and pain at the injection site. After 1 year, 20 of 39 patients were still under treatment with a positive effect. CONCLUSION: Treatment with BoNT-A injections led to a significantly greater improvement compared with placebo, according to patients' opinion and clinical assessment scales. Weakness in the hand is an important side effect of BoNT-A injections, but despite this disadvantage, most patients preferred to continue treatment. About 50% of our patients were still under treatment after 1 year.

Interobserver variation in the interpretation of SSEPs in anoxic-ischaemic coma.

OBJECTIVE: To study interobserver variation in the interpretation of median nerve SSEPs in patients with anoxic-ischaemic coma. METHODS: SSEPs of 56 consecutive patients with anoxic-ischaemic coma were interpreted independently by 5 experienced clinical neurophysiologists using guidelines derived from a pilot study. Interobserver agreement was expressed as kappa coefficients. RESULTS: Kappa ranged from 0.20 to 0.65 (mean 0.52, SD 0.14). Disagreement was related with noise level and failure to adhere strictly to the guidelines in 15 cases. The presence or absence of N13 and cortical peaks caused disagreement in 5 cases each. For recordings with a noise level of 0.25 microV or more, mean kappa was 0.34; for recordings with a noise level below 0.25 microV mean kappa was 0.74. CONCLUSIONS: Interobserver agreement for SSEPs in anoxic-ischaemic coma was only moderate. Since the noise level strongly influenced interobserver variation, utmost attention should be given to its reduction. If an artefact level over 0.25 microV remains, absence of N20 cannot be judged with sufficient certainty and the SSEP should be repeated at a later stage. SIGNIFICANCE: Because of its moderate interobserver agreement, great care has to be given to accurate recording and interpretation of SSEPs before using the recordings for non-treatment decisions.

Brainstem reflexes: electrodiagnostic techniques, physiology, normative data, and clinical applications.

An overview is provided on the physiological aspects of the brainstem reflexes as they can be examined by use of clinically applicable neurophysiological tests. Brainstem reflex studies provide important information about the afferent and efferent pathways and are excellent physiological tools for the assessment of cranial nerve nuclei and the functional integrity of suprasegmental structures. In this review, the blink reflex after trigeminal and nontrigeminal inputs, corneal reflex, levator palpebrae inhibitory reflex, jaw jerk, masseter inhibitory reflex, and corneomandibular reflex are discussed. Following description of the recording technique, physiology, central pathways, and normative data of these reflexes, including an account of the recording of recovery curves, the application of these reflexes is reviewed in patients with various neurological abnormalities, including trigeminal pain and neuralgia, facial neuropathy, and brainstem and hemispherical lesions. Finally, simultaneous electromyographic recording from the orbicularis oculi and the levator palpebrae muscles is discussed briefly in different eyelid movement disorders.

Thixotropy of levator palpebrae as the cause of lagophthalmos after peripheral facial nerve palsy.

Patients with facial nerve palsy are at risk of developing corneal ulceration because of lagophthalmos (incomplete closure of the affected eyelid). Lagophthalmos could result from thixotropy of the levator palpebrae muscle--that is, the formation of tight crossbridges between the actin and myosin filaments of the muscle fibres causing stiffness of the muscle--rather than from paralysis of the orbicularis occuli muscle as previously supposed. This possibility was investigated in 13 patients with a peripheral facial nerve palsy in a prospective open study. The levator muscle of the affected eyelid was stretched by manipulation and downward movement of the passively closed upper eyelid for approximately 15 seconds. The amount of lagophthalmos was measured before and immediately after this manoeuvre. In all patients except one there was a clear reduction in lagophthalmos (mean reduction 72%; range 60-100%). Thus in this setting the lagophthalmos appears to be caused by thixotropy of the levator palpebrae muscle, which has implications for treatment.

Clinical and neuropsychological correlates of the P300 in schizophrenia.

We investigated the relationship between the P300, neuropsychological test performance and symptomatology in recent-onset schizophrenic patients (n = 45) to gain insight into underlying mechanisms of abnormal P300 in schizophrenia. The P300 was recorded in two sessions with an intermission of five minutes, at the midline frontal, central and parietal electrode site. P300 amplitude and latency were compared with those obtained in 25 controls. Twenty patients were treated with olanzapine and 19 patients with risperidone. P300 amplitude was smaller and latency longer in patients than in controls. In the patient group, parietal P300 amplitude reduction was related to poorer performance on neuropsychological tests of memory. Frontal P300 amplitude reduction was related to impaired selective attention. In patients with negative symptomatology, P300 amplitude was reduced in the second P300 session compared with the first. Patients on risperidone demonstrated a smaller parietal P300 amplitude than patients using olanzapine. Reduced parietal P300 amplitude could signify a dysfunction in the continuous memory updating of current events. Negative symptomatology may be associated with a time dependent decrease in neuronal firing, as indicated by reduced P300 amplitude in the second P300 session.

Orbicularis oculi and orbicularis oris reflexes in blepharospasm and torticollis spasmodica during spasm-free intervals.

To investigate possible abnormalities of the blink reflex pathways, we analyzed the latencies and amplitudes of the blink reflex responses in the orbicularis oculi (Ooculi) muscle, following supraorbital nerve stimulation, in 19 patients with blepharospasm, 16 patients with torticollis spasmodica and 22 control subjects. Furthermore, in order to examine the suprasegmental control of the responses, the reflex responses were also evoked in the orbicularis oris (Ooris) muscle after stimulation of the ipsilateral supraorbital nerve. The responses were recorded only when subjects had no contractions of the eyelid muscles, either involuntarily, voluntarily or spontaneously; this could be controlled by a sound signal. The metrics of the reflex responses in the Ooculi and Ooris muscles in patient groups were comparable to those in controls. Our data indicate that the afferent and efferent pathways of the reflex arc and the suprasegmental control of the reflex are intact in patients with blepharospasm and torticollis spasmodica, at least during spasm-free intervals. Alterations of responses may occur during spasms due to either segmental or suprasegmental changes.

Somatosensory evoked potentials in very preterm infants.

OBJECTIVE: Cross-sectional and longitudinal reference values of cortical N(1) peak latency of the median nerve SEP in very preterm infants. METHODS: In infants in a placebo control group within an L-thyroxine supplementation trial, born at less than 30 weeks' gestation, cortical N(1) peak latency was measured at 2 weeks, at term and at 6 months corrected age. Cross-sectional N(1) latency values obtained in 50 infants and complete series of longitudinal values obtained in 15 infants were analyzed in relation to postmenstrual age (PMA). RESULTS: Mean N(1) latency decreased from 66 ms at 2 weeks to 38 ms at term and 20 ms at 6 months corrected age. Possible confounding factors did not have any significant effect on N(1) latency at 2 weeks or at term age except cranial ultrasound abnormalities at 2 weeks of age. CONCLUSIONS: Longitudinal N(1) latency values were consistent with cross-sectional N(1) latency values. The observed N(1) latency at term and at 6 months corrected age suggest that extrauterine maturation of the somatosensory pathway in infants born at less than 30 weeks' gestation is delayed by extrauterine life.

Blink reflexes and lateral spreading in patients with synkinesia after Bell's palsy and in hemifacial spasm.

We compared various electrodiagnostical tests in patients with hemifacial spasm and in patients who developed synkinesia after Bell's palsy. We examined the evoked blink reflexes in the orbicularis oculi (o. oculi) and orbicularis oris (o. oris) muscles in 23 patients with hemifacial spasm (HFS), in 10 patients with synkinesia after Bell's palsy (BPS) and in 22 control subjects. In the patient groups, we recorded synkinesia, latency and amplitude of compound muscle action potential (CMAP) in the mental muscle after stimulation of the facial nerve and we examined electromyographic activity of the o. oculi and mental muscles synchronously. Furthermore, we studied the phenomenon of lateral spreading, also known as ephaptic transmission, between the different facial nerve branches. Patients with BPS had a prolonged R1 latency on the affected side in o. oculi and smaller mental CMAP amplitude as an indication of facial nerve damage and nerve fiber loss. This was not found in patients with HFS, who showed an increased amplitude of the R1 and R2 responses in o. oris. Patients with BPS showed only an increased R1 amplitude in o. oris. All patients had signs of synkinesia. Lateral spreading with different patterns was present in all patients with HFS and in half of the patients with BPS. Latencies of early and late responses showed no differences between HFS and BPS. In addition to alterations in facial nucleus excitability in both conditions, ectopic re-excitation of facial nerve axons in HFS may explain the differences in neurophysiological findings between HFS and BPS patients. A loss of control following synaptic stripping may also be a contributing factor.

Determinants of quantitative spectral electroencephalography in early Alzheimer's disease: cognitive function, regional cerebral blood flow, and computed tomography.

Electroencephalography (EEG) bands may have different clinical or physiological correlates at initial diagnosis of Alzheimer's disease (AD). We studied 163 consecutive patients with probable (n = 105) and possible (n = 58) AD with measurements of cognitive function (CAMCOG), regional cerebral blood flow (rCBF) with single photon emission computed tomography using technetium-99m-labeled hexamethylpropylene amine oxime, and computed tomography (CT). Lower CAMCOG scores were significantly and most strongly associated with lower parieto-occipital and fronto-central alpha power. In a separate analysis of cognitive domains, disturbances in language, praxis, attention, and abstraction were also significantly and most consistently related to decrease in alpha power. Presence of cortical atrophy as measured on CT showed some statistically significant relations with EEG bands, but these associations were not consistent. Lower temporal and parietal rCBF were significantly related to lower parieto-occipital alpha activity. Presence of leukoaraiosis was significantly associated with lower beta values, but also with higher absolute theta and delta activity. The results suggest that alpha on EEG is most closely linked to cognitive function and rCBF, while beta and theta activity more likely reflect lower cortical or subcortical changes. Our study thus provides evidence that the EEG bands reflect differential pathophysiologic changes in AD.

Neuropsychological and clinical correlates of antisaccade task performance in schizophrenia.

OBJECTIVES: To elucidate pathophysiologic mechanisms involved in abnormal antisaccade task performance in schizophrenia by investigating a possible relationship among antisaccade task performance, neuropsychological test results, and symptomatology in a group of young patients with recent-onset schizophrenia; to compare the effects of olanzapine and risperidone on antisaccades and reflexive saccades. BACKGROUND: Patients with schizophrenia consistently perform worse than controls on the antisaccade task in which the subject is required to inhibit a reflexive saccade to a suddenly appearing visual target and look in the opposite direction. METHODS: In 37 young (mean age 21 years), medicated patients with recent-onset schizophrenia the authors assessed antisaccades, reflexive saccades, neuropsychological test performance, and symptomatology. A subgroup of 18 patients was treated with olanzapine, and 15 patients were treated with risperidone. Reflexive-saccade and antisaccade task results were compared with those obtained in 13 control subjects. RESULTS: The antisaccade error rate was significantly higher in the patients than in the control subjects. In the patients, poor working memory function was related to increased antisaccade error rate. Severity of disorganization symptoms at intake was related to prolonged mean latency of the correct antisaccades. Patients on risperidone had a prolonged mean latency in the reflexive saccade task compared with patients using olanzapine. CONCLUSIONS: Abnormal antisaccade task performance is already present in early schizophrenia and may reflect working memory dysfunction. In future studies, medication effects should be considered in interpreting eye movement test results of patients with schizophrenia.

Neurophysiological aspects of eye and eyelid movements during blinking in humans.

The neural relationships between eyelid movements and eye movements during spontaneous, voluntary, and reflex blinking in a group of healthy subjects were examined. Electromyographic (EMG) recording of the orbicularis oculi (OO) muscles was performed using surface electrodes. Concurrently, horizontal and vertical eye positions were recorded by means of the double magnetic induction (DMI) ring method. In addition, movement of the upper eyelid was measured by a specially designed search coil, placed on the upper eyelid. The reflex blink was elicited electrically by supraorbital nerve stimulation either on the right or the left side. It is found that disconjugate oblique eye movements accompany spontaneous, voluntary as well as reflex blinking. Depending on the gaze position before blinking, the amplitude of horizontal and vertical components of the eye movement during blinking varies in a systematic way. With adduction and downward gaze the amplitude is minimal. With abduction the horizontal amplitude increases, whereas with upward gaze the vertical amplitude increases. Unilateral electrical supraorbital nerve stimulation at low currents elicits eye movements with a bilateral late component. At stimulus intensities approximately two to three times above the threshold, the early ipsilateral blink reflex response (R(1)) in the OO muscle can be observed together with an early ipsilateral eye movement component at a latency of approximately 15 ms. In addition, during the electrical blink reflex, early ipsilateral and late bilateral components can also be identified in the upper eyelid movement. In contrast to the late bilateral component of upper eyelid movement, the early ipsilateral component of upper eyelid movement appears to open the eye to a greater degree. This early ipsilateral component of upper eyelid movement occurs more or less simultaneously with the early eye movement component. It is suggested that both early ipsilateral movements following electrical stimulation do not have a central neural origin. Late components of the eye movements slightly precede the late components of the eyelid movement. Synchrony between late components of eyelid movements and eye movements as well as similarity of oblique eye movement components in different types of blinking suggest the existence of a premotor neural structure acting as a generator that coordinates impulses to different subnuclei of the oculomotor nucleus as well as the facial nerve nucleus during blinking independent from the ocular saccadic and/or vergence system. The profile and direction of the eye movement rotation during blinking gives support to the idea that it may be secondary to eyeball retraction; an extra cocontraction of the inferior and superior rectus muscle would be sufficient to explain both eye retraction and rotation in the horizontal vertical and torsional planes.

An electro-myographic study of the distal porcine ureter.

PURPOSE: The accumulation of urine in the renal pelvis causes depolarisation of non-specific muscular pace-maker cells. The wave of depolarisation spreads distally in the ureteric smooth muscle cells via gap junctions. This wave of excitation causes a coordinated peristaltic contraction which transports the urine bolus distally to the bladder. The EMG activity in the distal porcine ureter was studied and analyzed to establish the characteristics of ureteric excitation. MATERIALS AND METHODS: Ten female New Yorkshire pigs (50 to 60 kg.) were studied in two groups under light halothane anesthesia (5% at induction and 1% for maintenance anesthesia). In both groups each pig was studied in two separate sessions at a week's interval. In group I (n = 5), bipolar needle electrodes (o: 0. 09 mm.) were implanted through a lower mid-line abdominal incision in the posterior bladder wall, the trigone and the pelvic ureter at intervals of 3 and 8 cm., respectively, from the ureteric orifice. In group II (n = 5), EMG spike burst activity was studied using a twin bipolar ring-electrode attached to an endoluminal ureteric catheter. EMG complexes were recorded using 0 to 30 Hz filters. The duration of spike burst complexes and their intervals were analyzed using a Nicollet, Pathfinder II(R) machine and a Poly(R) 4.9 digital signal processing program. RESULTS: Two types of spike burst activity could be distinguished between the electrodes: A, the migrating type and B, the non-migrating type. Frequency distribution analysis of spike burst duration revealed two main classes in experimental group II, a short spike burst (96%) which lasted 4.5 +/- 1.8 seconds and a longer one lasting 13.4 +/- 1.5 seconds. The conduction velocity of the migrating spike bursts (n = 177, 42% of total) between the proximal and the distal electrode had an average of 2.3 +/- 1.3 cm./sec. No relationship was found between the duration of the proximal spike burst and the conduction velocity. Data from experimental group I correlated well with data from group II. CONCLUSIONS: The results of our EMG study in the distal ureter reveal an approximately 9 cm. long electrically active zone in >/= 90% of EMG activity recordings. The duration of activity was approximately 5 seconds. Such an excited segment of ureter led to a contraction which occluded the ureter and could prevent retrograde leakage of intraluminal contents.

Soleus H-reflex tests in causalgia-dystonia compared with dystonia and mimicked dystonic posture.

Dystonia in the causalgia-dystonia syndrome is characterized by a fixed dystonic posture. To identify involvement of central pathophysiologic mechanisms, we analyzed soleus H-reflex tests in five patients with causalgia-dystonia. Soleus H-reflex test results in these patients differed from those in healthy controls but were similar to those in purely dystonic patients and healthy controls mimicking dystonic posture. The results suggest involvement of supraspinal mechanisms in the abnormal posture of causalgia-dystonia.

Correlation between electromyographic reflex and MR imaging examinations of the trigeminal nerve.

BACKGROUND AND PURPOSE: Previous studies have shown that clinical localization of trigeminal nerve lesions is inaccurate as compared with MR imaging findings. The purpose of our study was to ascertain the added value of electromyographic (EMG) investigation of the trigeminal nerve reflexes for the improvement of lesion localization and for the preselection of patients for MR imaging. METHODS: We reviewed the EMG studies of the trigeminal reflexes and the MR imaging studies of 20 patients with unilateral symptoms and signs related to the trigeminal nerve (40 trigeminal nerves examined). The results of the two studies were compared to assess the value of EMG in predicting MR imaging outcome. Lesion localization as demonstrated by EMG was compared with localization at MR imaging. MR imaging was used as the standard of reference. RESULTS: Eight (40%) of 20 patients had MR imaging findings related to presenting trigeminal symptoms, including five brain stem lesions and three peripheral lesions. Fourteen (70%) of 20 patients had EMG abnormalities related to presenting symptoms and signs. For brain stem lesions, lesion localization as shown by EMG corresponded well with MR imaging findings. EMG yielded a sensitivity of 100%, a specificity of 81%, a positive predictive value of 57%, and a negative predictive value of 100% in predicting MR imaging results. Interobserver agreement was good for both the EMG reflex and MR imaging examinations. CONCLUSION: Our data suggest that EMG recordings of the trigeminal reflexes can be used to exclude structural lesions in patients with symptoms related to the trigeminal nerve. When a lesion is localized in the brain stem with EMG, a tailored MR imaging examination of this region may be sufficient.

The diagnostic value of electroencephalography in mild senile Alzheimer's disease.

OBJECTIVE: We investigated the diagnostic value of the visually assessed electroencephalogram (EEG) in patients with mild Alzheimer's disease (AD), using the grand total of EEG (GTE) score. METHODS: Forty-nine non-demented control subjects with and without minimal cognitive impairment from the general population and 86 probable AD patients (NINCDS-ADRDA criteria), consecutively referred to a memory clinic, participated in this study. RESULTS: Frequency of rhythmic background activity (P<0.05), diffuse slow activity (P<0.001), and reactivity of the rhythmic background activity (P<0.001) were statistically significant related to the diagnosis control subject or AD patient, using logistic regression analysis with adjustment for age and sex. When these subscores were used to confirm the diagnosis of AD, thus at high specificity of 89.1% (GTE cut-off point of 3), the sensitivity was 44.6% and positive predictive value was 88.1%. Incremental ruling-in and ruling-out curves showed a maximum diagnostic gain of 38% for a positive test result at a prior probability ranging from 30 to 40%. At high pretest probability levels of 80-90%, the diagnostic gain for a positive test result was low, varying from 7 to 14%. CONCLUSION: In conclusion, the visually assessed EEG may give a clinically meaningful contribution to the diagnostic evaluation of AD when there is diagnostic doubt.