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.

Homozygous R788W point mutation in the XPF gene of a patient with xeroderma pigmentosum and late-onset neurologic disease.

The second Caucasian xeroderma pigmentosum patient (XP42RO) belonging to complementation group F (XP-F) is described. Mild ocular photophobia was present from childhood, and acute skin reactions occurred upon exposure to sunlight. Basal and squamous cell carcinomas developed after his twenty-seventh year. In his late forties progressive neurologic symptoms emerged, which included intellectual decline, mild chorea and ataxia, and marked cerebral and cerebellar atrophy. Such neurologic abnormalities are very unusual in XP-F. Similar symptoms have been described in only one of 17 other XP-F individuals. His approximately 5-fold reduced activity of nucleotide excision repair in cultured cells, combined with moderately affected cell survival and DNA replication after UV exposure, are typical of XP-F. The recent cloning of the XPF gene allowed a molecular genetic analysis of this unusual patient. XP42RO, representing the second case studied in this respect, turned out to be homozygous for a point mutation in the XPF gene, causing an R788-->W substitution in the encoded protein. Surprisingly, this mutation had also been found in one allele of the other unrelated Caucasian XP-F case. The amount of mutated XPF protein is strongly reduced in cells from XP42RO, presumably due to a conformational change. Biochemical, genetic, and clinical data all indicate the presence of considerable residual repair activity, strongly suggesting that the R788W mutation is leaky.

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.

Fitness to drive a car after recovery from severe head injury.

Driving skills in relation to residual psychologic impairments were studied in a sample of patients who had survived severe head injuries several years earlier. Daytime driving was studied in an instrumented car that recorded lateral position control on a highway track and during rides in the subjects' own cars with a professional observer. In comparison with a control group matched by age and driving experience, the patients performed worse on both driving tasks. In addition, the patient group showed clear impairments on a neuropsychologic test battery, despite the long intervals since their injuries. However, the only relationships found between test performance and driving involved visuomotor ability and lateral position control. No relationship was found between neurologic status and driving skill. The results are discussed in terms of patients' compensatory potential.

Meige syndrome: double-blind crossover study of sodium valproate.

A double-blind crossover study of sodium valproate and placebo was conducted in five patients with Meige syndrome. CSF neurotransmitter studies were performed at the end of each treatment period. GABA levels were not influenced by the administration of sodium valproate. An increase in HVA levels was observed in every patient, which may reflect an increase in central dopaminergic activity. This finding may explain the trend towards clinical deterioration which was observed during treatment with sodium valproate. Sodium valproate appears to be ineffective in Meige syndrome.

Signs of focal posterior cerebral abnormality in early subacute sclerosing panencephalitis.

In 16 cases of subacute sclerosing panencephalitis (SSPE), praxis and visual spatial capacities were more impaired early in the disease than were language functions. Together with the electroencephalographic findings, this suggests that the early lesions in SSPE are more pronounced in the parietooccipital area than in the classic language areas. Other reports also support such a localization. Detection of the disease in its early phase when dressing apraxia and visual impairment predominate is important in conducting clinical trials of different therapeutic agents.

Delayed deterioration following mild head injury in children.

A series of 42 children is described who, following a seemingly minor or trivial head injury, developed neurological signs after a lucid or symptom-free period. This group constitutes 4.34 per cent of 967 consecutive patients aged 2 months to 17 years who were seen by members of the neurological staff during the years 1978-1981. Only one patient had an intracranial haematoma. The majority of patients showed a benign transient syndrome consisting of either convulsive or nonconvulsive signs with a spontaneous and full recovery. There were, however, 3 deaths in this series, apparently due to severe and uncontrollable unilateral or diffuse brain swelling, demonstrating the malignant counterpart of this benign syndrome. The theories seeking to explain these phenomena are reviewed. Special reference is made to the hypotheses of Bruce and his associates regarding brain swelling as a causative factor. It is considered that an adequate theory to explain the pathogenesis is still lacking. It is concluded that the juvenile brain responds to cranial trauma in a manner different from the adult brain. This implies a different approach in policy to hospital admission.