B.W. Ongerboer de Visser

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

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

Neuropsychological and clinical correlates of antisaccade task performance in schizophrenia.

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

Pretarsal application of botulinum toxin for treatment of blepharospasm.

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.

Peripheral nerve abnormalities in adrenomyeloneuropathy: A clinical and electrodiagnostic study

Article abstract-Adrenomyeloneuropathy (AMN) is one of the two 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 carriers 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 no 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. NEUROLOGY 1996;46: 112-118

Phenotype of Charcot–Marie–Tooth disease Type 2

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

Soleus H-reflex tests and clinical signs of the upper motor neuron syndrome.

Soleus H-reflex tests are used for elucidating pathophysiological mechanisms in motor control. The cumulative vibratory inhibition of the soleus H-reflex, the ratio of the reflex to direct muscle potential (H to M ratio) and the recovery curve of the soleus H-reflex were studied in 38 patients with varying signs of the upper motor neuron syndrome for a possible relation with clinical features. The results were compared with those obtained from a group of healthy volunteers. The magnitude of vibratory inhibition decreased with increase of hypertonia. The H to M ratio increased as the activity of the tendon reflex was enhanced and correlated to a lesser degree with muscle tone. Both the H to M ratio and late facilitation of the soleus H-reflex recovery curve were elevated in clonus. The findings suggest that alterations in the results of soleus H-reflex tests relate to specific clinical features of the upper motor neuron syndrome. Possible pathophysiological implications are discussed.

Motor persistence of orbicularis oculi muscle in eyelid‐opening disorders

Article abstract—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.

Genetic linkage of hereditary motor and sensory neuropathy type I (Charcot-Marie-Tooth disease) to markers of chromosomes 1 and 17

Hereditary motor and sensory neuropathy type 1 (HMSN I) is an autosomal dominant disorder genetically localized on chromosome 1 in a few families and on chromosome 17 in other families. We analyzed linkage between 6 markers of chromosome 1, 2 markers of chromosome 17, and the HMSN I locus using restriction fragment length polymorphisms and serotyping for the Duffy blood group in 5 families with HMSN I. Only in 1 of these families is linkage present between the disease locus and the loci for Duffy blood group and glucocerebrosidase (chromosome 1 markers). In the 4 other families the HMSN I locus is linked to the chromosome 17 markers pEW301 and pA10–41.

The flexor carpi radialis H-reflex in polyneuropathy: relations to conduction velocities of the median nerve and the soleus H-reflex latency.

In 80 controls latencies of flexor carpi radialis (FCR) and in 94 controls latencies of soleus H-reflexes correlated well with length of the extremity, body height and age. Multiple regression equations using latency as a variable dependent on age and body height can be best used in practice when both reflexes are employed for demonstration of proximal pathology. The majority (69%) of 93 patients with various polyneuropathies showed abnormalities in both reflexes illustrating that proximal nerve segments are frequently involved. Four per cent had abnormal FCR H-reflexes with normal soleus H-reflexes whereas the reverse was found in 19% of the patients. Abnormal FCR H-reflexes occurred with normal motor and sensory conduction velocities in the peripheral part of the median nerve in 14%, whereas the reverse was seen in 12%, indicating that FCR H-reflex examination is a valuable supplement to conventional conduction studies for detection of electrophysiologically existing pathology.

Cerebrospinal fluid tumour markers in patients treated for meningeal malignancy.

The results of cerebrospinal fluid (CSF) biochemical markers were compared with conventional CSF cytology in patients treated for leptomeningeal metastases from extra cranial malignancies. For lumbar CSF, before treatment, no statistically significant difference of the probabilities of being positive was found between CSF cytology and a classification by linear discriminant analysis, based on patients age, of beta-glucuronidase and beta 2-microglobulin. During treatment, classification by linear discriminant analysis was found more often positive than cytology. Possible mechanisms for this difference are discussed. For ventricular CSF a correlation was found between CSF cytology and beta-glucuronidase for solid tumours, and between CSF cytology and beta 2-microglobulin for haematological malignancies. Reference values for ventricular protein, CEA beta-glucuronidase and beta 2-microglobulin were obtained for cytological negative samples.