High-dose intravenous immunoglobulin in the treatment of Guillain-Barré syndrome: a preliminary open study.

We report the effects of intravenous gamma-globulin (IVGG) in severe Guillain-Barré syndrome (GBS) in a small open study. Seven patients were given IVGG (0.4 g/kg/day) for 5 consecutive days. At the start of treatment all had progressing limb weakness and none could stand unaided. Within 24 h all but one patient started to improve, without the expected plateau phase, and progress was maintained with a mean time to independent walking of 14 days. One patient started treatment 9 h prior to ventilation for 15 days but was walking independently 31 days after admission. This study provides further evidence that IVGG is a promising therapeutic alternative to plasmapheresis in GBS. The rapidity of the response to IVGG raises the possibility that a single dose regimen might be equally or more effective.

An unusual neurological disorder of copper metabolism clinically resembling Wilson's disease but biochemically a distinct entity.

A patient with progressive neurological disease resembling Wilson's disease but in whom Kayser-Fleischer rings were absent, was given 67Cu and 64Cu, orally and intravenously, to measure the rate of absorption of copper using a convolution integral. The data show an abnormal distribution of body copper resulting in low copper concentrations in plasma, urine and liver but with an accumulation in the lower bowel probably due to a defect in mucosal transport. The importance of differentiating this condition from Wilson's disease is stressed.

The treatment of Parkinson's disease.

The treatment of Parkinson's disease is discussed. Levodopa is the most effective drug in this therapy. The place of other agents is discussed.

Kantamaneni BD, Curzon G:Comparison of benefit from L-dopa in Parkinsonism with increase of amine metabolites in the CSF.

Homovanillic acid (HVA) and 5-hydroxy indole acetic acid (5-HIAA) concentrations have been estimated in the cerebrospinal fluid (CSF) of 16 and 18 patients respectively with Parkinsonism both before and during treatment with l-dopa. The rise of HVA correlated with dose of l-dopa. An increase of HVA concentration to less than 0·10 µg/ml. was associated with little or no clinical improvement. The five patients with the greatest increase of HVA concentration/g l-dopa showed little or no improvement from treatment and four of these patients had normal pre-treatment HVA and 5-HIAA. In those patients who responded well to l-dopa the CSF HVA/g l-dopa was intermediate between that of these two groups. It is suggested that change in HVA content of CSF during l-dopa treatment might be of value in the prediction of response to l-dopa.

The mechanoreceptors of the costo-vertebral joints.

1. Unitary recording in the thoracic dorsal roots of mechanoreceptor discharges from the costo-vertebral joints was carried out in the cat and rabbit. Criteria for the identification of costo-vertebral joint mechanoreceptors were established.2. The majority of rib joint mechanoreceptors are slowly adapting and fifty-three such receptors were studied. Five rapidly adapting receptors were also identified.3. The responses of these receptors have been correlated with rib position and movement. The slowly adapting receptors gave a monotonic response to different rib positions. 72% showed an increase of discharge rate with displacements towards expiratory rib positions.4. In response to manually imposed rib movements slowly adapting joint mechanoreceptors gave a dynamic response which was directly related to the velocity of the movement and adapted within 2 sec. The movements of breathing produced a corresponding alteration of the discharge frequency of the slowly adapting receptors.5. Slowly adapting receptors were localized to the capsule of the costo-transverse joint by probing. They responded to increased intra-articular pressure with an increase of discharge rate and were silenced by intra-articular lignocaine, 0.4%.6. Rapidly adapting joint mechanoreceptors responded to rib movement with a brief burst of discharges.7. The rib joint mechanoreceptors signal rib joint position, and the direction and velocity of rib movement. It is suggested that these afferent discharges provide the basis for the perception of respiratory movements of the chest. The significance of these receptors to the ;sense of effort' resulting from a resistance to breathing is discussed.

Persistent phenothiazine dyskinesia treated with tetrabenazine.

Six patients with persistent phenothiazine dyskinesia were treated in a double-blind controlled trial with tetrabenazine 100 mg in divided dosage. In three patients the abnormal movements were abolished and in two others there was some improvement, but this was no greater than that achieved with the diazepam control. Tetrabenazine may be useful in the treatment of some patients with persistent phenothiazine dyskinesia.

Observations on radiation myelopathy.

Three cases of radiation myelopathy are reported. Corticosteroid therapy was associated with worth-while remissions in 2 patients. Two patients showed swelling of the spinal cord in myelograms and in one it extended below the irradiated part of the spinal cord. Demyelination of the dorsal white columns of the spinal cord unaccompanied by vascular abnormality was seen below the irradiated part of the cord. It is suggested that radiation damages the endothelial cell barrier of capillaries and arterioles after a latent interval. Proteinous oedema fluid spreads through the white matter from the capillaries and also into the arteriolar walls narrowing these vessels enough to cause local ischaemia and infarction. It is further suggested that apart from ischaemia and infarction myelin is also damaged by poor nutrition associated with oedema fluid, and that radiation damage to oligodendroglial cells is not the cause of this additional demyelination in patients with radiation myelopathy.

Comparison of the effects of bromocriptine and levodopa in Parkinson's disease.

The effects of bromocriptine and levodopa were compared in a blind trial in 18 patients with Parkinson's disease. Optimal doses of the two drugs were given in identical capsules: there was no significant difference between the therapeutic effects. There were wide individual differences in response to the two drugs. Side effects were more common with bromocriptine because of side effects.

Incidence of side effects from levodopa during the introduction of treatment.

Twenty patients with Parkinsonism were investigated in order to establish whether the gradual introduction of treatment with levodopa allows a higher dose to be tolerated than can be achieved if treatment is introduced rapidly. No indication was obtained that slow introduction of treatment offers an advantage in maximum tolerated dose, and patients aged 65 and over responded similarly in this respect to those under 65. The maximum tolerated dose is slightly lower in the elderly patient. The incidence of the different side effects does not appear to be affected by the rate of increasing the dose of levodopa.

Effect of age and arteriosclerosis on the response of Parkinsonian patients to levodopa.

Twenty-four patients with Parkinsonism were treated with levodopa for up to one year. Ten were aged under 65, 12 were aged 65 or over, and two were specifically included because they were considered to have arteriosclerotic Parkinsonism. These two patients showed no response to treatment. The 10 younger patients showed less clinical evidence of arteriosclerosis than the older ones, and responded significantly better to treatment with levodopa. Mean improvement was 61% in the younger group after 12 months' treatment and 28% in the older group. Improvement was greatest within three months of starting treatment. Abnormal movements which resulted from treatment with levodopa could be reduced with only slight loss of therapeutic benefit by the addition of tetrabenazine.

The assessment of drug treatment of spastic gait.

The technique of polarised light goniometry was used to quantify objectively parameters of the spastic gait during a double-blind cross-over trial comparing the spasmolytic effects of DS103-282, baclofen and placebo. Only minimal objective and subjective changes in gait were found when the results of treatment with DS103-282 or baclofen were compared with those of treatment with placebo.

Transient global amnesia in four brothers.

The case histories are described of four brothers who suffered attacks of transient global amnesia. The coincidence of this disorder in four siblings suggests that the causative factors in transient global amnesia may have a familial basis and that its incidence is more common than generally realised.

Osteomalacia presenting as chorea.

A 16-year-old epileptic developed chorea. He had osteomalacia, hypocalcaemia, and hyperphosphataemia, which were due not to hypoparathyroidism but to vitamin D deficiency--itself secondary to longstanding dietary deficiency and anticonvulsant drug administration.

Diffuse Lewy body disease: clinical features in 15 cases.

Fifteen cases of diffuse Lewy body disease were diagnosed on pathological grounds during a single year in one health district. The range and frequency of clinical features contrast strikingly with previous reports. The majority of cases presented with classical levodopa-responsive Parkinson's disease either alone (6 cases) or with mild cognitive impairment (3 cases); the remaining 6 cases presented with cognitive impairment alone. In time almost all patients developed both dementia and Parkinsonism. The dementia was cortical in type, but unusual in that most (12 cases) showed day-to-day fluctuation in severity at some point in their illness. These findings suggest that diffuse Lewy body disease is not rare, and that it presents in a range of ways from dementia with subsequent Parkinsonism to Parkinson's disease with subsequent dementia. The latter mode of presentation suggests that it should be considered as a significant pathological substrate of dementia in Parkinson's disease.

Diffuse Lewy body disease: an important differential diagnosis in dementia with extrapyramidal features.

Fifteen cases of diffuse Lewy body disease were identified in a systematic survey of all 216 brains referred to this hospital from a single health district in a single year. These cases presented with Parkinson's disease (40%), cognitive impairment (40%) and both (20%). Quantitative neuropathological studies using anti-ubiquitin immunocytochemistry revealed that dementia severity was related to cortical Lewy body density. The prevalence of diffuse Lewy body disease may have been underestimated in the past because of the neuropathological difficulties in making the diagnosis. Firstly, cortical Lewy bodies have a subtle appearance and are easy to overlook. Secondly, senile plaques are a common feature of diffuse Lewy body disease and may lead the unwary to make an erroneous diagnosis of Alzheimer's disease or "plaque-only Alzheimer's disease'. Diffuse Lewy body disease is a common and important cause of parkinsonian dementia, including the dementia of Parkinson's disease itself.

Familial autosomal dominant dopa responsive Parkinson's disease in three living generations showing extreme anticipation and childhood onset.

We describe a three generation family with Parkinson's disease showing autosomal dominant inheritance with extreme anticipation. Familial Parkinson's disease in three living generations is extremely rare, and anticipation is an unusual and interesting feature. Anticipation was shown in all generations and may have involved previous generations. Some cases of familial Parkinson's disease may therefore involve a trinucleotide repeat gene as part of the causal mechanism.

The form and distribution of the surface evoked responses in cerebellar cortex from intercostal nerves in the cat.

1. The form and distribution of the cerebellar evoked responses to electrical stimulation of intercostal and other thoracic segmental nerves were investigated in anaesthetized cats.2. Low intensity stimulation (< 2 x nerve threshold) evoked short latency, low amplitude (< 20 muV), initially surface positive responses which could only be distinguished with certainty from the electrocorticogram with averaging.3. On the basis of experiments involving sectioning of afferent tracts it is concluded that intercostal evoked responses of less than 7.0 msec latency are conducted in dorsal spino-cerebellar, ventral spino-cerebellar and dorsal column (cuneo-cerebellar) pathways.4. The surface positive waves have a highly punctate distribution with a steep potential gradient extending over an area of about 1 mm diameter. It is postulated that these small fields represent activation of single or few mossy fibre inputs.5. Short latency responses to thoracic inputs were found only in the ipsilateral intermediate cortex and lateral margin of the vermis of the anterior lobe (lateral two thirds of Larsell's lobules IV and V of the accessible cortex). The responses were distributed throughout the fore and hind limb areas of the anterior lobe and no rostro-caudal or medio-lateral segmental organization was seen.6. It is suggested that the overlapping distribution of thoracic and fore and hind limb mossy fibre inputs within the cerebellar cortex provides an anatomical basis for the integration of information from the trunk and from the limbs.

Smoking and Parkinson's disease.

In a case control study of the relationship between smoking habits and Parkinson's disease a negative association was demonstrated with a relative risk of 0 x 52. A history of smoking up to 20 years earlier was associated with a risk of developing Parkinson's disease equal to about half that in non-smokers. The type of disease, age of onset and rate of progression were associated with a similar reduction in risk implying that in respect of smoking history the disease is homogeneous. The positive correlation of degenerative vascular disease with smoking is further evidence that arteriosclerosis is not involved in the causation of Parkinson's disease. The negative association between Parkinson's disease and smoking is confirmed and is independent of other associated factors. The known and serious risks of smoking far outweigh the possible benefit of lowered risk of Parkinson's disease.