[Three infants with constipation and muscular weakness: infantile botulism]. / 3 zuigelingen met obstipatie en hypotonie: infantiel botulisme.

Two previously healthy infants, a boy of 10 weeks and a girl of 4 months presented with apathy and muscle weakness. A third previously healthy child, a girl of 6 weeks old was admitted with respiratory insufficiency. None of the three had had a bowel movement for a number of days. After extensive investigations which revealed few abnormalities Clostridium botulinum toxin was obtained in serum from all three children. Type-B-toxin was shown in the faeces of the older girl and boy; both recovered quickly. The other girl had type-A toxin; she died. Two of the three children were given honey to comfort them. Infantile botulism must be considered in every infant with symptoms of constipation and hypotonia. The diagnosis can quickly be confirmed by electromyography with repetitive 50-Hz-stimulation. Honey is a well-known source of the C. botulinum spore and should not be given to children under the age of 12 months. These three children are the first cases to be described in the Netherlands.

P300 component identification using source analysis techniques: reduced latency variability.

P300 latency variability in normal subjects is a complicating factor in clinical event-related potential studies because it limits diagnostic applicability. The current study was conducted to determine whether identification of P300 (P3A and P3B) components using source analysis techniques can reduce variability in P300 parameters. Data were recorded with a 128-channel EEG system in 18 healthy subjects. The authors used a standard, auditory two-tone oddball paradigm with targets of 2000 Hz and standards of 1000 Hz. Two simple source analysis models with one or two rotating dipoles were applied to grand average data and individual data. Dipole time courses were combined with mapping results to extract P3A and P3B component latencies. Latencies obtained with conventional P300 analysis were compared with source analysis results. The source analysis method identified both P3A and P3B components in a substantially larger percentage of subjects (88% vs. 33%) than the conventional method. The source analysis method yielded a later mean P3B latency (357 msec vs. 323 msec, P < 0,001) with a smaller standard deviation (9 msec vs. 23 msec, P = 0,003) than the conventional P300 method. The relative contribution of the temporally separate P3A and P3B components to the P300 complex amplitude is highly variable. This explains the larger latency standard deviation in conventional P300 analysis. The source analysis method was able to identify P300 components in a large percentage of the cases. The result is a considerable reduction of P300 latency variability in normal subjects. This could have important consequences for clinical event-related potential research, because diagnostic sensitivity and specificity of P300 latency may improve with this method.

[Hemifacial spasms caused by neurovascular compression]. / Hemifaciale spasmen door neurovasculaire compressie.

Three patients, one woman aged 52 years and two men aged 63 and 71 years, respectively, had involuntary movement on one side of their face due to hemifacial spasms. The first patient's spasms were misdiagnosed as a tic, the second patient had received injections of botulinum A toxin which gave no improvement and the third patient suffered from persistent symptoms after a first neurovascular decompression without intraoperative EMG monitoring. All three patients underwent microvascular decompression of the facial nerve with intraoperative EMG monitoring. All three patients were cured. Hemifacial spasm is a curable illness if appropriately diagnosed and treated. Oral medications have no effect on the disease. Local injection of botulinum A toxin is indicated when the spasm is mild or when surgery is contraindicated. The primary causative factor is vascular compression of the facial nerve at its exit zone. Therefore, decompressive surgery is the logical treatment, and the best results are obtained with intraoperative EMG monitoring.

The prognostic value of serial EEG recordings following acute neonatal asphyxia in full-term infants.

Perinatal asphyxia is one of the major causes of non-progressive neurological deficits seen in children. It is reported that currently no set of parameters allowing for accurate prediction of prognosis following severe perinatal asphyxia is available. Even electroencephalogram (EEG) recordings, which are known to give a fairly good prediction of long-term outcome, have their flaws. The aim of this prospective study was to evaluate the additional value of serial EEGs in full-term infants. In all, 36 infants were enrolled. All met strict entrance criteria, received standard treatment and underwent two EEGs according to a pre-set protocol: the first between 12 and 36 hours post-partum, the second between 7 and 9 days post-partum. It is clearly demonstrated that serial EEG recordings do enhance the prognostic value of the EEG. Moreover, distinct progression seen in serial EEGs is highly prognostic for a normal outcome and has even more prognostic value than one single severely abnormal EEG. A better indication of future outcome is obtained from serial EEGs.

Primary lateral sclerosis: clinical, neurophysiological, and magnetic resonance findings.

OBJECTIVE: To describe the clinical, neurophysiological, and MRI findings in 10 patients with primary lateral sclerosis (PLS). RESULTS: The course of the disease was very slowly progressive. Spasticity due to upper motor neuron dysfunction was the most prominent sign, but EMG showed slight lower motor neuron signs, such as a mixed pattern on maximal voluntary contraction and enlarged motor unit potentials. One patient had clinically mild lower motor neuron involvement. Central motor conduction times (CMCT) were more prolonged in PLS than is the case in ALS. Minor sensory signs were found on neurophysiological examination, comparable with those in ALS. In four patients serum creatine kinase activity was raised. On MRI cortical atrophy was seen, most pronounced in the precentral gyrus and expanding into the parietal-occipital region. CONCLUSIONS: PLS is a distinct clinical syndrome, part of the range of motor neuron diseases. Besides pronounced upper motor neuron symptoms, mild lower motor neuron symptoms can also be found, as well as (subclinical) sensory symptoms. PLS can be distinguished from ALS by its slow clinical course, a severely prolonged MEP, and a more extensive focal cortical atrophy.

Opsoclonus-induced occipital deactivation with a region-specific distribution.

The cerebral distribution of 2-[18F]fluoro 2-deoxy-D-glucose (FDG) uptake in a patient with opsoclonus was measured by positron emission tomography (PET) and subsequently compared with the distribution in ten normal subjects. Statistical parametric mapping (SPM) revealed a decreased occipital FDG uptake in the patient, particularly at the posterior bank of the parieto-occipital sulcus (putative visual area PO/V6), in the region ventrally bordering V5, and anterolaterally in the calcarine sulcus. Such a specific pattern of occipital deactivation may indicate that opsoclonus suppresses the processing of visual motion along the magnocellular pathway. This is in agreement with normal saccadic suppression which has been proposed to contribute to the perception of a stable visual space.

Hemifacial spasm: intraoperative electromyographic monitoring as a guide for microvascular decompression.

OBJECTIVE: Microvascular decompression is the logical and well-accepted treatment of choice for hemifacial spasm (HFS). In experienced hands, good to excellent results can be obtained. However, sometimes the exact site of the vascular compression is unclear. The aim of this study was to analyze whether intraoperative monitoring by stimulated electromyography of the facial nerve may help to improve the results of vascular decompression for HFS. METHODS: In a series of 74 patients operated for HFS, the impact of intraoperative facial nerve monitoring on the surgical procedure was analyzed by use of the clinical and operative patient records. The role of this type of monitoring, with assessment of the so-called abnormal muscle response, was broken down into four categories: a guiding, a confirming, an indirect confirming, or an inconclusive role. The relationship between abnormal muscle response monitoring results and final surgical outcome was analyzed. RESULTS: The overall cure rate was 87.8%, including patients who had previously undergone unsuccessful operations. Complications were minor, and hearing impairment was found in 2.7% of patients. A guiding role of intraoperative monitoring was apparent in 33.8% of patients, and a confirming role was demonstrated in 52.7% of patients, which resulted in a positive contribution of approximately 87% for intraoperative facial monitoring in microvascular decompression for HFS. In patients defined as guiding cases, the cure rate was 92%. CONCLUSION: This study demonstrates the applicability and usefulness of intraoperative facial nerve monitoring in microvascular decompression operations for HFS.

Hyperthermic isolated regional perfusion of the limb with carboplatin.

AIMS: To investigate the feasibility of hyperthermic isolated regional perfusion (HIRP) with carboplatin in the management of locally recurrent and/or intransit metastases of melanoma or locally advanced soft tissue sarcoma. METHODS: Three patients, two with locally advanced melanoma and one with a low-grade liposarcoma of the lower extremity, were treated with HIRP under mild hyperthermia (39-40 degrees C) with 125 mg carboplatin/l perfused limb volume. RESULTS: No systemic toxicity was observed. Local toxicity consisted of post-perfusion oedema present in all three patients which resolved within 2 weeks. Clinically, a persistent local neuropathy was observed in all three patients, two of which were confirmed by electromyogram and nerve conduction study. Severe motor-sensory neuropathy was located mainly in the peroneal and sural nerves of the perfused limbs. Pharmacokinetic parameters of the carboplatin showed a higher concentration of carboplatin in the skin compared to the muscle. The two melanoma patients showed a complete response but developed local recurrences within 1.5 years after perfusion. The third patient underwent a delayed excision of the sarcoma 8 weeks after perfusion which revealed 50% viable tumour. One of the melanoma patients and the sarcoma patient died from lung metastases 56 and 31 months post-perfusion treatment, respectively. The other melanoma patient is alive 95+ months post-perfusion treatment. CONCLUSIONS: The local neurotoxicity observed did not warrant further research of carboplatin in HIRP.

Mild axonal neuropathy of children during treatment for acute lymphoblastic leukaemia.

Neurophysiological functioning was studied prospectively in children treated for acute lymphoblastic leukaemia with a low dose vincristine regime (8 x 1.5 mg/m2/dose), to obtain more insight into vincristine neuropathy. A WHO neurotoxicity score was estimated and vibration sense and electrophysiological measurements were taken at standardized times during vincristine treatment. The WHO neurotoxicity score showed decreased or disappearance of Achilles tendon reflexes, and mild sensory disturbances, but a grade 3-4 neurotoxicity was not demonstrated by any of the children. Vibration perception thresholds increased progressively during treatment and amplitudes of action potentials of peroneal and sensory ulnar and median nerves decreased, whereas nerve conduction velocities stayed unchanged. Both vibration perception thresholds and the electrophysiological findings hardly exceeded the limits of normality. We conclude that children treated for acute lymphoblastic leukaemia with a low dose vincristine regimen have mild axonal neuropathy which may be responsible for the motor problems in these children.

Botulinum toxin versus trihexyphenidyl in cervical dystonia: a prospective, randomized, double-blind controlled trial.

BACKGROUND: Botulinum toxin type A (BTA) is replacing trihexyphenidyl as the treatment of choice for idiopathic cervical dystonia (ICD), but there has never been a direct comparative study. METHODS: This trial compares the effectiveness of BTA with that of trihexyphenidyl in a prospective, randomized, double-blind design. Sixty-six consecutive patients with ICD were randomized to treatment with trihexyphenidyl tablets plus placebo injection or placebo tablets plus BTA injections. Tablets were administered daily according to a fixed schedule. Dysport or saline was injected under EMG guidance at study entry and again after 8 weeks. Patients were assessed for efficacy at baseline and after 12 weeks by different clinical rating scales. RESULTS: Sixty-four patients completed the study, 32 in each group. Mean dose of BTA was 292 mouse units (first session) and 262 mouse units (second session). Mean dose of trihexyphenidyl was 16.25 mg. The changes on the Disability section of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-Disability) (primary outcome), Tsui Scale, and the General Health Perception Subscale were significantly in favor of BTA. More patients treated with BTA had an improvement of at least three points on the TWSTRS-Disability (14 versus 6) and on the Tsui Scale (23 versus 12). Adverse effects were significantly less frequent in the BTA group. CONCLUSION: BTA is significantly more effective in the treatment of ICD, with less adverse effects.

Hereditary myokymia and paroxysmal ataxia linked to chromosome 12 is responsive to acetazolamide.

A sixth family with autosomal dominantly inherited myokymia and paroxysmal ataxia is described. The syndrome in this family is linked to the recently discovered locus for inherited myokymia and paroxysmal ataxia on the human chromosome 12p, and a missense mutation is shown in the KCNA1 gene. The attacks of ataxia in this family compare well with those of previously described families and similarly are precipitated by kinesigenic stimuli, exertion, and startle. Responsiveness of these attacks to low dose acetazolamide is confirmed, but some loss of efficacy occurs with prolonged treatment, and side effects are notable. Although not all affected family members showed myokymia on clinical examination, electromyography invariably showed myokymic discharges, in one patient only after a short provocation with regional ischaemia. One affected family member also had attacks of paroxysmal kinesigenic choreoathetosis, responsive to carbamazepine.

Unique myoclonic pattern in corticobasal degeneration.

We describe two similar patients with a clinical diagnosis of corticobasal ganglionic degeneration (CBGD). After a period of increased action tremor, both patients developed a fixed posture in the right arm with a slow rhythmic myoclonus, which appeared to be caused by trains of highly synchronized and stimulus sensitive myoclonic discharges. Resetting of the spontaneous myoclonic discharges by peripheral and central stimulation and a jerk-locked cortical potential were demonstrated in one case. The somatosensory evoked potentials (SEPs) showed abnormal parietal curves with small N20-P25 amplitudes and without giant SEP characteristics. The latencies of the cortical event and of the late responses, and the duration and distribution of the discharges compare best with those of the cortical reflex type of myoclonus. Localized parietal cortical damage, as indicated by clinical evidence and imaging techniques, may well explain the absence of a giant SEP in these patients with CBGD.

Idiopathic spasmodic torticollis: a survey of the clinical syndromes and patients' experiences.

We evaluated the medical and psychosocial experiences of 59 patients with idiopathic spasmodic torticollis (ST) by means of a structured questionnaire. The results generally corresponded with those of other studies in the literature. Diagnosis is delayed in many patients, and ST negatively influences the patients' social lives. Because drug treatment and physiotherapy are only of sufficient value in a minority, most patients seek benefit from numerous other therapies, none of which has been shown to improve ST.

Muscle fiber conduction velocity in the diagnosis of familial hypokalemic periodic paralysis--invasive versus surface determination.

Muscle fiber conduction velocity (MFCV) in the brachial biceps muscle was determined in a large family of patients with hypokalemic periodic paralysis (HOPP) by both a surface and an invasive method. Other surface EMG parameters and the muscle force were also determined. Both the surface and the invasive method showed a significantly lower mean MFCV in the proven gene carriers but only the invasive method showed a lower MFCV in all proven carriers. It can be concluded that MFCV determination is a reliable method to detect the membrane defect in HOPP carriers and that the invasive method is not only easy to perform, but also more sensitive. The muscle force and the integrated EMG at maximal voluntary contraction were lower in the carrier group. A positive correlation between the surface MFCV and the neuromuscular efficiency (the quotient of force and integrated EMG) was found in the controls but not in the HOPP carriers. Since type II fibers have a higher neuromuscular efficiency, this suggests a preferential involvement of type II fibers in HOPP.

Muscle fiber conduction velocity in amyotrophic lateral sclerosis and traumatic lesions of the plexus brachialis.

Muscle fiber conduction velocity (MFCV) in biceps brachii was studied in traumatic brachial plexus lesions (16 patients) and amyotrophic lateral sclerosis (ALS) (22 patients) by means of an invasive (I-MFCV) and a surface (S-MFCV) method. After complete denervation an exponential decrease of the mean I-MFCV was found, T1/2 = 1.1 month. After 4-5 months this resulted in severely reduced conduction velocities (mean 1.4 m/sec, range from 0.5 to 2 m/sec). Simultaneous with signs of reinnervation, fibers with faster conduction velocities were seen. In ALS, a decrease of the mean I-MFCV was found, and slow conducting fibers were found in every patient on at least one side. At the same time muscle fibers with increased I-MFCVs were found. This increased range of velocities seems based on a combination of slow conducting, atrophic fibers, with fast conducting, hypertrophic fibers, compensating the force loss. In some subjects we found these disturbances without clear abnormalities with concentric needle EMG, and with unimpaired muscle force. The surface EMG measurements in the ALS patients revealed increased S-MFCV values in combination with a decrease of the median frequency (Fmed). We suggest that the opposite finding of an increased S-MFCV is a consequence of the muscle fiber hypertrophy in the surviving, voluntarily recruited, motor units. The simultaneous decrease of the Fmed seems to be caused mainly by the change in shape of the motor unit potential.

Toxicity of hyperthermic isolated limb perfusion with cisplatin for recurrent melanoma of the lower extremity after previous perfusion treatment.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) has been shown to be effective for locoregional metastases or local recurrent disease. Locoregional recurrences after previous HILP is an unsolved problem. METHODS: HILP with cisplatin, 20-30 mg/l perfused limb volume, was performed in seven patients with recurrent melanoma (five with Stage IIIA and two with Stage IIIAB) after previous HILP with melphalan with or without dactinomycin. A cisplatin perfusion without local excision was performed in four patients; this treatment resulted in two complete responses and one partial response. In three patients, a cisplatin perfusion was performed with local excision of the in-transit metastases. RESULTS: During a median follow-up of 20 months (range, 10-25 months), in five (83%) patients the tumor recurred locally after a median period of 5 months (range, 3-11 months). No systemic toxicity was observed. Local toxicity consisted of postperfusion edema and neurotoxicity in all patients. The edema resolved within 2 weeks, which was in contrast to persistent neurotoxicity. A severe motor-sensory neuropathy was observed in three (43%) patients and mild sensory neuropathy in four (57%) patients. CONCLUSIONS: The severe neurotoxicity and the high local recurrence rate do not justify the use of HILP with cisplatin for recurrent melanoma after previous HILP with melphalan with or without dactinomycin.

Long-lasting supernormal conduction velocity after sustained maximal isometric contraction in human muscle.

Local muscle fatigue (1 min maximal voluntary contraction) and recovery were studied by means of surface and invasive EMG on elbow flexors to record the changes in muscle fiber conduction velocity (MFCV), median power frequency (MPF), integrated EMG (IEMG), and force. The main finding was a long-lasting "supernormal" MFCV during recovery, for at least 1 hour. After a normalization phase, the MFCV and MPF continued to increase reaching a steady state at supernormal values after 10-12 min. Mean MFCV increase at 20% MVC after 15-min recovery was 0.58 m.s-1 (12%). Postfatigue IEMG values were increased at all contraction levels. In combination with near normal force levels, this resulted in a decrease in "neuromuscular efficiency" (force/IEMG). We suggest that this IEMG increase is mainly a result of the MFCV increase. The MFCV changes in fastest and slowest fibers found with the invasive method indicate a relatively equal effect on type I and II fiber types. A possible explanation of the supernormal MFCV is muscle fiber swelling, in combination with altered membrane properties.

Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves.

The clinical, electrophysiological, radiological and morphological data of 3 members of a family with autosomal dominant distal spinal muscular atrophy (DSMA) are reported. One patient has the clinical picture of peroneal muscular atrophy with atrophic calves. His father and sister suffer from cramps and fasciculations of the calves with true neurogenic muscular hypertrophy of the calves. The electromyogram and the biopsy specimen are conclusive for motor neuron disease in this family. These findings suggest that the DSMA variant as described by D'Alessandro et al. (Arch. Neurol. (1982) 39: 657-660), concerning benign spinal muscular atrophy with hypertrophy of the calves, has to be considered as a mild manifestation of DSMA.

Familial paroxysmal kinesigenic ataxia and continuous myokymia.

A large family with paroxysmal ataxia and continuous myokymic discharges is described. The disorder is of autosomal dominant inheritance. During attacks coordination of movements and balance are disturbed; often a postural tremor of the head and the hands and fine twitching in some of the facial and hand muscles are present. The attacks usually last a few minutes and may occur several times per day. They first appear in childhood and tend to abate after early adulthood. The attacks are frequently precipitated by kinesigenic stimuli similar to those in paroxysmal kinesigenic choreoathetosis. Their occurrence can be reduced or prevented by carbonic anhydrase inhibitors. Between attacks a slight postural tremor and ataxia was found in a few of the elderly affected members. Fine rippling myokymia was obvious in a few and could be detected on close inspection in about half of the adults. Electromyography (EMG) showed myokymic discharges in all affected members. The characteristics and reactivity of this myokymic activity suggest multiple impulse generation in the peripheral nerves.