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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. [ABSTRACT FROM AUTHOR]

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.

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.

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.

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., (Copyright 2002 Wiley Periodicals Inc.)

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.

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.

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., (Copyright 2001 S. Karger AG, Basel)

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.

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.

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., (Copyright 2000 S. Karger AG, Basel)

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.

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., (Copyright 2000 S. Karger AG, Basel)

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.

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.

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.

Objective: To study the functional motor nerve supply of the upper esophageal sphincter in humans., Study Design: Intraoperative electromyographic study., Methods: The contribution of the recurrent laryngeal nerve and the pharyngeal plexus in the motor nerve innervation of the cricopharyngeal muscle and the inferior pharyngeal constrictor muscle was examined intraoperatively., Results: Electromyography showed that there is a considerable overlap in the innervation of the cricopharyngeal muscle and the inferior pharyngeal constrictor muscle. The recurrent laryngeal nerve functionally contributes to the motor innervation of the cricopharyngeal muscle in all patients and contributes to the motor innervation of the inferior pharyngeal constrictor muscle in most patients. The pharyngeal plexus functionally contributes to the motor innervation of the inferior pharyngeal constrictor muscle but does not always contribute to the motor innervation of the cricopharyngeal muscle., Conclusions: This is the first report which provides evidence that the recurrent laryngeal nerve functionally contributes to the motor innervation of the cricopharyngeal and inferior pharyngeal constrictor muscle. Furthermore, this study shows that intraoperative electromyography in humans is a feasible method to analyze the physiology of the motor innervation of the upper esophageal sphincter.

Unlabelled: Transcranial motor evoked potentials (tc-MEPs) are used to monitor spinal cord integrity intraoperatively. We compared myogenic motor evoked responses with electrical and magnetic transcranial stimuli during nitrous oxide/opioid anesthesia. In 11 patients undergoing spinal surgery, anesthesia was induced with i.v. etomidate 0.3 mg/kg and sufentanil 1.5 microg/kg and was maintained with sufentanil 0.5 microg x kg(-1) x h(-1) and N2O 50% in oxygen. Muscle relaxation was kept at 25% of control with i.v. vecuronium. Electrical stimulation was accomplished with a transcranial stimulator set at maximal output (1200 V). Magnetic transcranial stimulation was accomplished with a transcranial stimulator set at maximal output (2 T). Just before skin incision, triplicate responses to single stimuli with both modes of cortical stimulation were randomly recorded from the tibialis anterior muscles. Amplitudes and latencies were compared using the Wilcoxon signed rank test. Bilateral tc-MEP responses were obtained in every patient with electrical stimulation. Magnetic stimulation evoked only unilateral responses in two patients. With electrical stimulation, the median tc-MEP amplitude was 401 microV (range 145-1145 microV), and latency was 32.8 +/- 2.3 ms. With magnetic stimulation, the tc-MEP amplitude was 287 microV (range 64-506 microV) (P < 0.05), and the latency was 34.7 +/- 2.1 ms (P < 0.05). We conclude that myogenic responses to magnetic transcranial stimulation are more sensitive to anesthetic-induced motoneural depression compared with those elicited by electrical transcranial stimulation., Implications: Transcranial motor evoked potentials are used to monitor spinal cord integrity intraoperatively. We compared the relative efficacy of electrical and magnetic transcranial stimuli in anesthetized patients. It seems that myogenic responses to magnetic transcranial stimulation are more sensitive to anesthetic-induced motoneural depression compared with electrical transcranial stimulation.

Ureteric peristalsis transports a urinary bolus from the renal pelvis to the bladder. We developed an intraluminal catheter with a pressure transducer on it to study intraluminal pressure changes and a twin bipolar electrode to record the ureteric EMG and impedance (Z) changes during a peristaltic wave. Five female New Yorkshire pigs (50-60 kg) were studied under light halothane anesthesia (5% at induction/1% for maintenance). A steady state of hydration was maintained using intravenous saline infusion. EMG spike burst activity was studied at a 10-cm interval using low (0-30) Hz filters. Impedance between the same electrodes is measured simultaneously in higher frequencies (1-5 KHz) as a function of ureteric motor activity. Pressure generation in the ureteric lumen was also measured simultaneously by a transducer on the same catheter. A digital signal processing program (Poly 4.9) was used for analysis. Parenteral furosemide was used to induce diuresis. Resting ureteric impedance (Z(R)) decreases to Z(B) (Z bolus) during the passage of the urinary bolus. Passage of a contractile zone during a peristaltic wave increases impedance from Z(B) to its Z(R) level and initiates a pressure rise. Bolus length (the length Z(B)) is not constant and decreases distally. EMG corresponds well in time to impedance. Z(R) disappears after infusion of furosemide because of increased urine load and changes of intraluminal ionic environment. The contractile segment of a ureteric peristaltic wave appears to be represented by an elevated Z segment (Z(C)). Pressure rise is recorded only at the beginning of a contractile zone. A specially adapted intraluminal catheter can be used to study peristalsis in the upper urinary tract. One can study all the three components of ureteric peristalsis (excitation, contraction, and intraluminal pressure rise) using such a catheter.

Sufficient reference values for motor nerve conduction velocity (MNCV) in very preterm infants are not yet available. In the placebo infants within an L-thyroxine supplementation trial, born at less than 30 weeks' gestation, ulnar and posterior tibial MNCV measurements were performed shortly after birth. Repeated measurements were done at 2 weeks, at term, and at 6 months corrected age. Cross-sectional MNCV values obtained in 50 infants and longitudinal MNCV values obtained in 15 infants were analyzed in relation to postmenstrual age (PMA). Mean ulnar MNCV increased from 13 to 44 m/s and mean tibial MNCV from 11 to 37 m/s. Motor nerve conduction velocity was clearly related to PMA. Longitudinal MNCV values were consistent with cross-sectional MNCV values. Possible confounding factors did not have any significant effect on MNCV. In the ulnar nerve, extrauterine maturation during the first 2 weeks of life was delayed compared with intrauterine maturation.

The relation between quantitative spectral electroencephalogram (qEEG) parameters and subsequent rate of cognitive, functional, and behavioral decline in 82 consecutive patients with early probable Alzheimer disease (NINCDS-ADRDA criteria) was examined in a prospective study. The qEEG was performed at initial examination and global cognitive function, activities of daily living, and behavior were assessed at initial evaluation and after a period of 6 months. Using multiple linear regression analysis, higher frontocentral and parieto-occipital theta values, lower parieto-occipital beta values, and lower peak frequency were significantly associated with more decline in global cognitive function over the follow-up period. In addition, lower parieto-occipital beta values were significantly related to more decline in activities of daily living. These associations were independent of demographic (age, sex, and education) and disease characteristics [initial Cambridge Examination for Mental Disorders of the Elderly Cognitive test (CAMCOG) or Mini-Mental State Examination scores, estimated duration of symptoms, estimated prior rate of decline, and dementia severity]. In a separate multiple logistic regression analysis, prediction of rapidly progressive decline, defined as 8 or more points decline in CAMCOG scores (n = 21), could be made with parieto-occipital and frontocentral beta values. The results suggest that slowing on qEEG is a marker for subsequent rate of cognitive and functional decline in mildly demented AD patients, independent of demographic or disease characteristics.

We investigated whether an index based on clinical features, electroencephalogram and computed tomography is useful to predict survival in early Alzheimer's disease. One hundred and sixty-three consecutively referred patients to an outpatient memory clinic and first diagnosed with Alzheimer's disease (105 'probable' and 58 'possible', NINCDS-ADRDA criteria) were studied and outcome measure was death. Cox proportional hazards regression analysis and Kaplan-Meier survival curves were used to investigate relations between baseline parameters and survival. Eighty-four patients (51. 5%) died during the follow-up period that extended to 5.8 years, with a median duration of survival after entry of 4.3 years. Baseline factors that were statistically significant and independently related to increased risk of mortality were high age, male sex, poor cognitive function as measured with the CAMCOG, low alpha and beta power on electroencephalogram, and temporoparietal atrophy on computed tomography scan. These results were independent of the diagnosis probable or possible Alzheimer's disease. Based on the coefficients from the regression equation, we computed a survival index for each patient and we constructed three groups according to tertiles of this index. After 5.2 years of follow-up, survival curves showed a low mortality group with 81.7% patients alive (median survival at least 5.7 years), an intermediate mortality group with 35.9% patients alive (median survival 3.8 years), and a high mortality group with no patients alive (median survival 2.3 years). Log rank tests were statistically significant for comparisons between all three groups. We conclude that an overall index combining demographic, cognitive, electroencephalogram and computed tomography features is a strong predictor of survival in early Alzheimer's disease.

Background: The value of physical examination in detecting involved neck muscles in cervical dystonia (CD) is uncertain and little is known about changes in electromyographic (EMG) features after botulinum toxin type A (BTA) treatment., Methods: In a double-blind, randomized study we recorded the EMG activities of 420 neck muscles in 42 patients with CD before and after treatment with BTA or trihexyphenidyl. We regarded any needle EMG activity higher than 100 microV as the gold standard for involuntary involvement of a muscle in the dystonic posture and compared this with the results of physical examination. We calculated EMG total scores by adding the scores of the individual muscles., Results: Physical examination had a low predictive value in the detection of involved muscles. There was a significant correlation between changes in EMG total scores and changes in clinical measurements. We observed increased EMG activity in 20% of noninjected muscles after BTA treatment and in 27% of noninjected muscles after trihexyphenidyl treatment. A switch from one most active muscle to another was seen equally in both groups and had no influence on clinical response., Conclusion: Physical examination alone is not sufficient to detect involved muscles, and repeated, simultaneous EMG-guided application of BTA may be helpful. In addition to clinical measurements, changes in EMG activity due to treatment can be used as a physiologic measure in evaluating treatment response. Increased activity of noninjected muscles and a switch from one most active muscle to another are not related to BTA treatment, but are probably pathophysiologic phenomena of CD itself.

Functionally and anatomically, the orbicularis oculi (OO) muscle can be subdivided in a pretarsal, a preseptal, and an orbital portion. In the rhesus monkey, fluorescent and neuronal retrograde tracing experiments were performed in the pretarsal or the orbital portion of the OO muscle, or both, using fast blue, diamidino yellow, and wheat germ agglutinin-horseradish peroxidase as tracers. The preseptal portion was not investigated because of close anatomical relationships to the other portions. It was found that motoneurons innervating the OO muscle are located exclusively within the intermediate subnucleus of the motor facial nucleus. The upper pretarsal motoneurons show a specific distribution in the dorso-rostral border area of the intermediate subnucleus, representing a dome-like organization, while lower pretarsal motoneurons are situated more ventrally in the adjacent area. The pretarsal motoneurons are all located dorsally in the rostral half and the upper part of the caudal half of the intermediate subnucleus. The upper pretarsal portion is subserved by about one third of the total intermediate motoneuron population. The size of the upper pretarsal motoneurons is similar to that of the motoneurons of the lower pretarsal portion of the OO muscle and falls, for the vast majority, into the large motoneuronal range. Motoneurons belonging to the upper and lower orbital portions are located ventrally and are more randomly distributed in the rostral half of the intermediate subnucleus. The size of orbital motoneurons varies from small to large. The large fraction of pretarsal motoneurons may reflect the specific function of the upper pretarsal portion during rapid and highly coordinated movements of the eyelids in different types of blinking.

Objective: To evaluate the first clinical experience with local botulinum toxin A (BTA) injections in patients with writer's cramp., Design: Descriptive., Setting: Academic Medical Centre, Amsterdam, the Netherlands., Method: In May 1993-January 1996 ten patients with writer's cramp were treated with BTA (Dysport). Age of the patients varied from 28 to 68 years, the duration of complaints from 1 to 29 years. Muscles for injections were selected by observation, sometimes combined with electromyography. BTA was administered under electromyographic guidance., Results: The amount of BTA administered per treatment session ranged from 15 to 400 IU. In three patients the BTA-induced weakness necessary to reach a beneficial effect on writing was unacceptable. In seven patients the response was satisfactory or good and lasted 2 to 15 months (mean: 3.5 months)., Conclusion: The results confirm the efficacy of BTA in writer's cramp.

Objective: To determine whether measures of quantitative spectral electroencephalography (EEG) can predict survival in patients with early Alzheimer disease., Design: Prospective cohort study; median duration of follow-up was 4.4 years in survivors and 2.6 years in nonsurvivors. Cox proportional hazards models, with adjustment for age and sex were used to estimate relationships between EEG measures and survival. Log relative percentage values of EEG bands were used as predictors., Setting: Outpatient university memory clinic., Participants: One hundred one consecutively referred patients with early probable Alzheimer disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria were studied with EEG at the time of diagnosis. The mean age of the patients was 79.2 years, which was higher than in previous EEG studies., Main Outcome Measure: Mortality., Results: Fifty-one patients (50.5%) died during follow-up, with a median survival time in all patients of 4.1 years. The following EEG variables were significantly associated with increased risk of mortality: from parieto-occipital leads, higher theta (hazard ratio, 2.05; 95% confidence interval, 1.15-3.66; P<.05), lower alpha (hazard ratio, 0.43; 95% confidence interval, 0.25-0.76; P<.01), and lower beta (hazard ratio, 0.38; 95% confidence interval, 0.22-0.68; P<.001) activity; and from frontocentral leads, higher theta activity (hazard ratio, 2.07; 95% confidence interval, 1.17-3.66; P<.05). Stepwise Cox regression analysis showed that loss of parieto-occipital beta (P<.01) and alpha (P<.05) power were independent and significant predictors of mortality. Both beta (12.6-35.4 Hz) and alpha (7.5-12.5 Hz) activity remained significantly associated with mortality after adjustment for education, dementia severity, symptom duration, level of cognitive function, presence of extrapyramidal symptoms or hallucinations, presence of vascular risk factors, and presence of leukoaraiosis or local cortical atrophy., Conclusions: Decreases of beta and alpha activity on quantitative spectral EEG are independent predictors of mortality in patients with early Alzheimer disease. In the clinical context, the use of EEG technology for prediction of survival in individual patients remains to be determined.

Objective: To study the effect of L-thyroxine supplementation on neurologic maturation in very preterm infants with transient hypothyroxinemia., Design: Randomized, double-blind, placebo-controlled, L-thyroxine supplementation trial., Setting: Level III neonatal intensive care unit., Subjects: A total of 200 infants <30 weeks' gestational age., Intervention: Subjects were randomly assigned to receive L-thyroxine (8 microg/kg birth weight per day) or a placebo during the first 6 weeks of life., Methods: Median nerve somatosensory evoked potentials were recorded, measuring cortical N1 peak latency at 2 weeks of age, at term, and at 6 months (corrected) age., Results: Cortical N1 peak latency was not decreased significantly in the L-thyroxine group compared with the placebo group throughout the study period., Conclusion: L-Thyroxine supplementation during the first 6 weeks of life did not decrease cortical N1 peak latency in infants of <30 weeks' gestational age.

Background: Transient hypothyroxinemia is common in preterm infants and has been associated with neurodevelopmental dysfunction and slow nerve conduction velocity. It is still unknown whether L-thyroxine supplementation is required. During an L-thyroxine supplementation trial, motor nerve conduction velocity was measured to answer the question whether L-thyroxine supplementation improves motor nerve conduction velocity., Methods: Two hundred infants < 30 weeks' gestational age were enrolled in a randomized, double-blind, placebo-controlled L-thyroxine supplementation trial. L-Thyroxine (8 micrograms/kg birthweight per day) or a placebo was administered during the first 6 weeks of life. Motor nerve conduction velocity was measured in the ulnar and posterior tibial nerve shortly after birth, at 2 weeks, at 40 weeks, and at 66 weeks postmenstrual age., Results: At 2 weeks, the ulnar motor nerve conduction velocity had improved in the L-thyroxine group compared with the placebo group, although the difference was not statistically significant (difference between means: 0.8 msec; 95% CI: -0.13 to 1.80; p = 0.06). Later on, no effect of L-thyroxine supplementation on motor nerve conduction velocity was found., Conclusion: This study shows that in infants < 30 weeks' gestational age L-thyroxine supplementation during the first 6 weeks of life does not clearly improve motor nerve conduction velocity.

We report on a blink reflex abnormality observed in two patients, which provides additional information on the central pathways mediating this reflex. Autopsy was performed in one patient and MRI in the other. In the first patient there was a small lesion at the dorsal middle third of the lateral tegmental field and in the second patient at the level of the dorsal lower third of the medulla oblongata. In both patients the common finding was the absence of the late response (R2) ipsilateral to the side of the lesion, while the R2 response on the unaffected side was normal regardless of the side of the supraorbital nerve stimulation. The R1 responses were normal. This type of blink reflex abnormality has not been reported before and is referred to by us as 'tegmental type' of R2 abnormality. The results led to the conclusions that: (i) the crossed and uncrossed ascending trigeminofacial connections are mediated through the lateral tegmental field; (ii) the uncrossed trigeminofacial connection originates at the level of at least the lower medulla oblongata; (iii) the contralateral R2 response is established by way of an ascending pathway, which crosses the midline at the level of at least the lower third of the medulla oblongata.

In the cynomolgus monkey, motoneurons innervating the levator palpebrae superioris muscle form a nucleus within the oculomotor nuclei called the central caudal nucleus. After double fluorescent neuronal retrograde tracing experiments, using fast blue and diamidino yellow as tracers in the levator palpebrae superior muscles, labelled motoneurons (30%) were found in an unpaired central caudal nucleus. Approximately 2% of the labelled motoneurons were double-labelled. The labelled and double-labelled neurons were distributed randomly over the central caudal nucleus, lateralization of populations of levator motoneurons within this nucleus was not observed. The afferent innervation of the levator palpebrae superioris muscle was restricted to the ophthalmic branch area of the gasserian ganglion. Primary afferent labelled neurons were absent from the mesencephalic nucleus of the fifth nerve. Surprisingly, fast blue was also found in the ophthalmic branch area of the contralateral ganglion of Gasser, while diamidino yellow was present only ipsilaterally. About 1% of the afferent labelled neurons were double-labelled. The results reveal that in the cynomolgus monkey the central caudal nucleus is not only topographically but also functionally one nucleus. Afferent innervation of the levator palpebrae superioris muscle is probably bilaterally organized.

Forty-three former polio patients now complaining of new progressive muscle weakness (symptomatic patients) plus 13 former polio patients without new neuromuscular complaints were included in the study. The symptomatic patients reported high frequencies of other neuromuscular complaints and a decline in their functional level. Most frequent complaints were general fatigue, low backache, and muscle pain (97.7%, 86%, and 79.1%, respectively) and a decline in the ability to walk (80%). In a prospective follow-up averaging 2.1 years, the muscle strength of 26 muscles in all four limbs of each patient was assessed by manual muscle testing and was also measured isometrically using a handheld dynamometer. During the follow-up period, we did not find a significant decrease in muscle strength in the symptomatic patients as compared to patients without new neuromuscular complaints.

Two patients, men aged 82 and 53 years, with weakness of the facial muscles after surgery in the posterior fossa had keratitis caused by the inability to blink and to close the eye. Botulinum toxin type A was injected into the levator palpebrae superioris muscle under electromyographic control. A selective, reversible paralysis of this muscle was induced without weakness of the anatomically related rectus superior muscle. This botulinum toxin-induced protective ptosis appeared to be effective and safe in the treatment and prevention of keratitis in patients with a temporary weakness of the facial muscles.

A patient with neurofibromatosis type I and breast carcinoma developed a bilateral but asymmetric blepharospasm and paresis of the left abducens muscle over a 2-week course. MRI disclosed a small lesion in the left dorsomedial lower pontine region. Electrodiagnostic investigations revealed bilateral R1 responses after stimulation of the left supraorbital nerve and enhancement of R1 and R2 recovery curves. We concluded that lesions in the lower pontine tegmentum may cause blepharospasm.

Adrenomyeloneuropathy (AMN) is one of the most frequent phenotypes of X-linked adrenoleukodystrophy. Whether the polyneuropathy in AMN results from primary demyelination or axonal degeneration is uncertain. We examined 23 patients (18 men with AMN and five female carrier with AMN symptomatology), performed electroneurography and EMG, and compared our results with standardized electrodiagnostic criteria for primary demyelination. Both clinically and electrodiagnostically, the lower extremities were most frequently and most severely affected. A longer duration of symptoms was related to more severe pyramidal dysfunction (p < 0.004) and spasticity (p < 0.04), and to a more severe impairment of vibration sense (p < 0.05). There were on correlations between the different electrophysiologic studies and the duration of neurologic symptoms. Only two AMN patients (9%) fulfilled the electrodiagnostic criteria for primary demyelination. However, both had abnormally low compound muscle action potentials, which may have been a reflection of primary axonal degeneration. Six other patients (26%) partially fulfilled the criteria for primary demyelination, of whom five also manifested low compound muscle action potentials. In 15 patients (65%), we found polyneuropathy with predominantly axonal, sensorimotor features. We conclude that the neuropathy in AMN patients is due to primary axonal degeneration.

R1 and R2 blink reflex responses to single and paired stimuli were investigated in 23 control subjects, 21 patients with blepharospasm (BSP), 20 patients with torticollis spasmodica (TS), and 23 with hemifacial spasm (HFS). For paired stimuli, we compared measurements of area and peak responses at two and three times R2 threshold. R1 and R2 indices were calculated as the average of the recovery values at 0.5-, 0.3-, and 0.21-s interstimulus intervals to test individual patients. Peak amplitude measurements at three times R2 threshold were optimal. The R2 index was abnormal in 67% of BSP patients, 37% of TS patients, and 50% of HFS patients on the affected side and 20% on the unaffected side. A normal R2 index in one third of patients with BSP may indicate that different pathophysiological mechanisms are involved in this type of focal dystonia.

Extinction of the soleus H reflex at higher stimulus intensities is commonly attributed to retrograde conduction of action potentials in motor axons. This study was designed to gain further insight into the mechanisms underlying the extinction. The decrease of the H reflex was quantified in a group of controls and spastic patients, with and without depression of the H response by continuous tendon vibration. Response amplitudes were normalized as a percentage of the maximal M wave amplitude. Stimuli were normalized as a multiple of the M wave threshold. After normalization, the mean M recruitment curves, and similarly the fractions of motor axons activated, were equal in each group. In contrast, the mean H reflex amplitudes at the M threshold were different. The mean H reflex decrease, between 1.0 and 1.5 times the M threshold, was found to be the same fraction of the maximal H reflex amplitude in each group. The largest motor fibres, belonging to the largest motoneurones, are traditionally thought to have the lowest threshold for electrical excitation. Collision or retrograde inactivation should therefore preferentially affect the largest motoneurones, employed in only the largest H reflexes, at the lowest stimulus intensities. Our results are contrary to this hypothesis. Renshaw and/or Ib inhibition is likely to play a role in the initial decrease of the H reflex at higher stimulus intensities.

The response to botulinum toxin type A was compared after two injection techniques in 45 patients with blepharospasm. Initially, patients were treated according to a triple injection technique; two injections into the upper eyelid and one injection into the lower eyelid. Subsequently, without altering the dose, the same patient group received two further injections into the pretarsal portion of the orbicularis oculi muscle of the upper lid. Triple injections were given in 227 treatments, of which 81% were successful. Mean duration of benefit was 8.5 weeks. Additional pretarsal injections were given in 183 treatment sessions. The number of successful treatments significantly increased, to 95% (P < 0.001), and the mean duration of benefit increased to 12.5 weeks (P < 0.001). Ptosis occurred significantly less often after pretarsal injections (P < 0.01). Patients with combined blepharospasm and involuntary levator palpebrae inhibition responded better to the pretarsal injection technique.

Sixty patients with idiopathic cervical dystonia were treated a total of 240 times with botulinum toxin type A (BTA). Selected muscles were injected with BTA under electromyographic (EMG) guidance. The clinical effect was measured on the Tsui scale and a 10-point anchored visual analogue scale. A dosage of 150-300 mouse units was used in 77% of the treatments (mean 204 mouse units). Based on the Tsui scale, 45% of 240 treatments were still effective at the moment of reinjection (median improvement 2 points). Based on the 10-point anchored visual analogue scale, 73% of treatments were successful (median improvement 3 points). Forty-eight patients (80%) responded favourably to the treatment. Side-effects were mild and transient. Dysphagia occurred in 9% of treatments. Antibody production was investigated in 41 patients and was negative in all. A striking difference from previous reports is the lower dosage used in this study. The clinical response, however, was similar to that of other studies. We conclude that a dosage of 200-400 mouse units BTA (Dysport) may also be effective in the treatment of cervical dystonia, but with fewer side effects. EMG guidance and application of BTA into deep cervical muscles may further improve the clinical effect.

Electromyographic (EMG) activity of orbicularis oculi and levator palpebrae muscles was recorded to study the origin of involuntary eyelid closure in 33 patients. The evoked blink reflex in all patients and in 23 controls was also studied. To examine the excitability of facial motoneurons and bulbar interneurons in individual patients and to compare the results with EMG findings, R1 and R2 recovery indices were calculated in all subjects, as the average of recovery values at 0.5, 0.3, and 0.21 second interstimulus intervals. Based on EMG patterns, the patients were divided into three subclasses: EMG subclass 1, 10 patients with involuntary discharges solely in orbicularis oculi muscle; EMG subclass 2, 20 patients with involuntary discharges in orbicularis oculi and either involuntary levator palpebrae inhibition or a disturbed reciprocal innervation between orbicularis oculi and levator palpebrae; EMG subclass 3, three patients who did not have blepharospasm, but had involuntary levator palpebrae inhibition in association with a basal ganglia disease. The total patient group showed an enhanced recovery of both R1 and R2 components compared with controls. Although 30 out of 33 patients had blepharospasm (EMG subclasses 1 and 2), R1 recovery index was normal in 64% and R2 recovery index was normal in 54%. Patients with an abnormal R2 recovery index had an abnormal R1 recovery index significantly more often. All patients from EMG subclass 1 had an abnormal R2 recovery index, whereas all patients from EMG subclass 3 had normal recovery indices for both R1 and R2 responses. Seventy five per cent of the patients from EMG subclass 2 had normal recovery indices. The results provide further evidence that physiologically blepharospasm is not a homogeneous disease entity, and indicate that different pathophysiological mechanisms at the suprasegmental, or segmental level, or both are involved.

We describe clinical and EMG findings in three patients with an inability to reopen the eyes after voluntary closure of the eyelids. Synchronous EMG recording from the levator palpebrae (LP) and orbicularis oculi (OrbOc) muscles revealed that after voluntary closure of the eyelids and upon the command to open the eyes, all three patients were unable to inhibit the "voluntary" contraction of the OrbOc muscles, while on clinical examination there was no evidence of ongoing OrbOc muscle contraction. This "motor persistence" was restricted predominantly to the pretarsal portion of the OrbOc. In one patient, it occurred as an isolated abnormality of the eyelid movement and was recorded as an additional EMG abnormality in two patients with blepharospasm and involuntary LP inhibition. Clinical examination alone cannot differentiate this type of disorder of supranuclear control of eyelid movement from involuntary LP inhibition; simultaneous EMG recording from the LP and OrbOc muscles is required. Injection of botulinum toxin into the pretarsal portion of OrbOc muscles is helpful.

We studied the ratio of the maximal H-reflex to maximal direct muscle potential (H/M ratio), late facilitation and late inhibition in the recovery curve, and vibratory inhibition of the soleus H-reflex in three consecutive patients with hereditary dopa-responsive dystonia, before and during treatment with levodopa. In one patient, we repeated the H-reflex tests twice after withdrawal of levodopa. The results were compared with those in a group of 48 healthy subjects. In the patients before treatment, the soleus H-reflex recovery curve showed increased late facilitation and depressed late inhibition, reflecting alterations in postsynaptic interneuronal activity. Vibratory inhibition, predominantly reflecting presynaptic inhibitory action, was depressed. Normalization of these test results occurred during levodopa treatment, concurrent with a clear clinical response. The H/M ratio, reflecting the excitability state of the motoneuron pool, was similar during and without levodopa treatment. In the one patient tested after levodopa withdrawal, enhancement of late facilitation and decrease of vibratory inhibition paralleled the reoccurrence of dystonia most clearly. Since soleus H-reflex tests mainly reflect mechanisms operating at the spinal level, spinal aminergic or dopaminergic systems are probably involved in dopa-responsive dystonia.