[Familial hemiplegic migraine resulting in recurrent coma]. / Familiaire hemiplegische migraine als oorzaak voor recidiverend coma.

A 71-year-old woman presented with recurrent episodes of headache accompanied by hemihypoesthesia, fever, aphasia, reduced consciousness and worsening of pre-existing ataxia. Brain imaging revealed atrophy of the cerebellum. The white cell count in the cerebrospinal fluid was slightly increased. The patient had a family history of migraine and cerebellar ataxia. DNA testing revealed a missense mutation in the CACNA1A gene, confirming the diagnosis of familial hemiplegic migraine. Familial hemiplegic migraine is a rare subtype of migraine with aura. It follows an autosomal dominant pattern of inheritance. Patients with familial hemiplegic migraine exhibit a wide spectrum of symptoms, which can hinder the diagnosis. If a patient presents with recurrent coma or encephalitis with or without cerebellar ataxia, familial hemiplegic migraine should be included in the differential diagnosis.

[The restless legs syndrome can be treated with dopamine agonists]. / Het 'restless legs'-syndroom, te behandelen met dopamineagonisten.

In three patients, a man aged 46 years and two women aged 74 and 38 years, respectively, restless legs syndrome (RLS) was diagnosed. The second patient had a low serum ferritin concentration. The patients were successfully treated with ropirinol, iron suppletion and gabapentine, and pramipexol, respectively. With a prevalence of 7% in the general population, RLS is a frequent disease. Patients complain about unpleasant feelings in the legs and have an urge to move the legs, causing discomfort during rest. Sleep is disturbed significantly, which interferes with normal functioning of the patients during the day. RLS may be caused by anaemia, uraemia or as a side effect of drugs such as selective serotonin uptake inhibitors (SSRIs), lithium and tricyclic antidepressants. RLS can be treated successfully by dopaminergic agents, especially dopamine agonists.

[A man with the combination of dry and wet beriberi]. / Een man met de combinatie van droge en natte beriberi.

A 34-year-old alcoholic man had neurological and cardiac symptoms. The patient was admitted to the hospital for acute painful sensory disturbances and severe weakness of the feet. Neurological and electrophysiological investigation revealed axonal sensorimotor polyneuropathy that was most prominent in the legs. Cardiac assessment showed signs and symptoms of heart failure due to a high-output state. Blood analysis showed a low thiamine concentration of 58 nmol/l (lower reference limit: 80). Therefore, a diagnosis of combined wet beriberi with cardiomyopathy and dry beriberi with axonal polyneuropathy was made. The treatment of beriberi is simple and effective and consists of thiamine supplementation in conjunction with diuretic treatment. With this approach, the patient recovered fully. Patients with beriberi have a good prognosis, particularly when the diagnosis is made at an early stage.

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.

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.

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.

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.

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.

Retrograde tracing studies of subdivisions of the orbicularis oculi muscle in the rhesus monkey.

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.

Electromyography in cervical dystonia: changes after botulinum and trihexyphenidyl.

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.

Treatment of cervical dystonia: a comparison of measures for outcome assessment.

UNLABELLED: There is little agreement on which outcome measures to use to express the efficacy of treatments for cervical dystonia. We analyzed change scores on various scales of 64 new patients with cervical dystonia before and after repeated injections with botulinum toxin. METHOD: The association between change in impairment (Tsui), and change in pain (TWSTRS-Pain) and functional health (TWSTRS-D, MOS-20) was expressed in percentages of variance explained. Effect sizes of the outcome measures from patients who continued botulinum treatment and dropouts were compared. Performance of outcome measures to distinguish patients who continued treatment and dropouts was analyzed with ROC curves and areas under the curve (AUC). RESULTS: Impairments explained < or =7% of the score variance in functional health. There were no differences between the effect sizes of impairment and pain of patients who continued treatment and dropouts (p > 0.60). This suggests a poor reflection of the treatment efficacy by these outcome measures. Conversely, there were significant differences between the effect sizes of the functional status scales of the patients who continued treatment and the dropouts (p < or = 0.01). ROC curve analysis showed that the disability, handicap, and global disease burden scale accurately distinguished between the two groups (AUCs > 0.80). Impairments showed no discriminative accuracy (AUC = 0.46). CONCLUSION: Neurologic impairments have a small impact on the functional health of cervical dystonia patients. Disability, handicap, and a global measure of disease burden were the most suitable outcome parameters to express the clinical efficacy of botulinum therapy.

Long-term effect of botulinum toxin on impairment and functional health in cervical dystonia.

We investigated the long-term effect of botulinum toxin type A (BTA) on impairment as well as functional health in terms of disability, handicap, and quality of life in 64 patients with cervical dystonia. These patients, who first participated in a double-blind trial, were followed for another 12 months. Fifty-four patients continued treatment after 12 months of follow-up and showed improvement on all scales. Furthermore, this effectiveness appeared to increase during follow-up, which suggests a cumulative clinical effect of BTA.

The late blink reflex response abnormality due to lesion of the lateral tegmental field.

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.

A retrograde double fluorescent tracing study of the levator palpebrae superioris muscle in the cynomolgus monkey.

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.

Treatment outcomes in cervical dystonia: a clinimetric study.

We reviewed 21 studies (8 blinded and 13 open) on the treatment of botulinum toxin type A for cervical dystonia, directed to the health aspects used to evaluate the patients' response to treatment (Medline search 1985-1993, English language literature). The prerequisite for comparing the treatment results was that studies had to evaluate similar aspects of disease. The ICIDH model, outlined by the World Health Organization in 1980, orders the different health outcomes into distinct classes of disease consequences. Our aim was to order the health outcomes according to the model and, thus, to study the comparability of treatment outcomes. Three differences could be identified between the objective and the subjective instruments. (a) The aspects measured by the subjective instruments varied substantially; of the 22 different subjective instruments identified in 18 studies, 8 measured impairments, 5 disability, and 9 could not be classified according to the ICIDH model. The objective instruments measured impairments. (b) All objective instruments were multiitem, whereas only 2 of 22 subjective instruments could be identified as multiitem. (c) The subjective instruments were generally poorly documented with regard to the number of items, score range, or grading. We conclude that the treatment outcomes can only be compared on the objective level of assessment and with regard to the patients with painful dystonia. The subjective instruments, particularly those focusing on disease-specific disability, deserve further research. The ICIDH model offers a useful framework for selection, improvement, and development of outcome instruments. Because the model clearly demarcates the different consequences of disease, adoption will enhance the comparability of outcomes in cervical dystonia intervention trials.