Non-familial degenerative disease and atrophy of brainstem and cerebellum. Clinical and CT data in 47 patients.

We studied the clinical features of 47 patients with a non-hereditary degenerative disease and with atrophy of brainstem or cerebellum or both in CT scanning. There was no relation between the CT findings and duration or severity of the disease, nor with the kind of the neurological signs which comprised ataxia, a hypokinetic rigid syndrome, oculomotor abnormalities, upper and lower motor neuron signs, orthostatic hypotension and dementia. The 2 main diagnoses were olivopontocerebellar atrophy (OPCA), or a combination of OPCA and striatonigral degeneration (SND). The differential diagnosis with Parkinson's disease and progressive supranuclear palsy was discussed. We concluded, that a CT scan is warranted in all cases of suspected Parkinson's disease, especially in those without tremor, and in cases of motoneuron disease with broad-based gait. In our patients with mainly hypokinesia and rigidity, levodopa treatment had no or brief beneficial effects. If ataxia predominated, OPCA appeared the most sensible diagnosis; if a hypokinetic-rigid syndrome predominated, the diagnoses SND plus OPCA appeared the most suitable. We assessed the degree of atrophy on CT subjectively, because an interobserver study of 60 normal CT scans, did not produce reliable measurements.

Limbic encephalitis. A rare presentation of the small-cell lung carcinoma.

Two patients with an acute organic brain syndrome and accompanying neurological symptoms are described. Extensive work up showed that both patients suffered from small-cell lung cancer. Cerebral metastases were absent. Following chemotherapy and radiotherapy to the primary tumor one of the two patients showed a complete remission of psychiatric symptoms for one year. A paraneoplastic origin of this syndrome, in the literature known as limbic encephalitis, is postulated. The exact cause of this syndrome is yet unknown. Recent research reveals data indicating an immunological pathogenesis. The major clinical importance of this (neuro)-psychiatric syndrome is that its appearance may serve as a warning sign for an occult malignancy; furthermore, effective treatment of the primary malignancy can reverse the encephalitis. Thus antitumor therapy can result in a prolonged survival and considerably improved quality of life.

Induction of aromatic-L-amino acid decarboxylase by decarboxylase inhibitors in idiopathic parkinsonism.

We evaluated the effect of administration of L-dopa, alone or in combination with a peripheral decarboxylase inhibitor, on plasma levels of aromatic-L-amino acid decarboxylase (ALAAD). After single-dose administration of L-dopa plus benserazide (Madopar) in healthy subjects and in chronically treated patients with parkinsonism, plasma ALAAD followed for 2 to 3 hours fell, but returned to predosing levels within 90 minutes. Four groups of patients with idiopathic parkinsonism were studied during chronic treatment: Group I, no L-dopa treatment (n = 31); Group II, L-dopa alone (n = 15); Group III, L-dopa plus benserazide (n = 28); and Group IV, L-dopa plus carbidopa (Sinemet, n = 30). Plasma ALAAD 2 hours after dosing was normal in Groups I and II. ALAAD was increased threefold in Groups III and IV, suggesting induction of ALAAD by the coadministration of a peripheral decarboxylase inhibitor. In a study of 3 patients in whom L-dopa/benserazide was started, plasma ALAAD rose gradually over 3 to 4 weeks. Further detailed pharmacokinetic studies of L-dopa, dopamine, and ALAAD in plasma and cerebrospinal fluid are required to determine if the apparent ALAAD induction by a peripheral decarboxylase inhibitor may be related to the loss of clinical efficacy of combination therapy in some patients and how it is related to end-of-dose deterioration and on-off phenomena.

Treatment of idiopathic parkinsonism with L-dopa in the absence and presence of decarboxylase inhibitors: effects on plasma levels of L-dopa, dopa decarboxylase, catecholamines and 3-O-methyl-dopa.

The effect of levodopa (L-dopa), alone or in combination with a peripheral decarboxylase inhibitor (PDI), on plasma levels of aromatic-L-amino acid decarboxylase (ALAAD, = dopa decarboxylase), L-dopa, 3-O-methyl-dopa (3-OMD), dopamine (DA), noradrenaline, adrenaline and dopamine beta-hydroxylase has been studied. In healthy subjects and in patients with parkinsonism plasma ALAAD level fell after administration of L-dopa + benserazide, but returned to previous levels within 90 min. In a cross-sectional study blood was obtained, 2 h after dosing, from 104 patients with idiopathic parkinsonism, divided into four groups: no L-dopa treatment (group 1), L-dopa alone (group 2), L-dopa + benserazide (Madopar) (group 3) and L-dopa + carbidopa (Sinemet) (group 4). Plasma ALAAD, which was normal in groups 1 and 2, was increased 3-fold in groups 3 and 4, indicating that there was induction of ALAAD by the co-administration of PDI. Despite this induction of ALAAD, in groups 3 and 4, with half the daily L-dopa dose compared with group 2, plasma L-dopa and 3-OMD levels were 5 times higher, while plasma DA levels were not different. The DA/L-dopa ratio was decreased 5-fold in group 2 and 16-fold in groups 3 and 4 as compared with group 1. Neither 3-OMD levels nor 3-OMD/L-dopa ratios correlated with the occurrence of on-off fluctuations. In a longitudinal study of three patients started on Madopar treatment the induction of plasma ALAAD was found to occur gradually over 3-4 weeks. Further detailed pharmacokinetic studies in plasma and cerebrospinal fluid are required in order to elucidate whether the ALAAD induction by PDI may be related to the loss of clinical efficacy of combination therapy in some patients and how it is related to end-of-dose deterioration and on-off phenomena.

Spatial contrast sensitivity in unilateral cerebral ischaemic lesions involving the posterior visual pathway.

Contrast sensitivity function was studied in 16 patients with unilateral ischaemic lesions involving the posterior visual pathway. Sixty-two percent of the patients showed contrast sensitivity loss in at least one eye for horizontal or vertical stimulus orientation. Visual perception was distorted in a qualitatively different way according to the anteroposterior site of the lesion. Patients with occipital or occipitotemporal lesions showed high spatial frequency selective losses and patients with temporal or parietal lesions low frequency selective losses. Stimulus orientation selectivity was observed in patients with lesions of the primary visual cortex as well as in patients with lesions anterior to the striate cortex. Contrast sensitivity orientation-selective losses were demonstrated in 14 of the 17 'affected' eyes.

Pulmonary function in Parkinson's disease.

Pulmonary function was investigated in 31 consecutive patients with relatively severe Parkinson's disease. Clinical disability was assessed by Hoehn and Yahr scale, Northwestern University Disability Scale and Websterscore. All patients were on levodopa substitution therapy and used anticholinergics. Pulmonary function was investigated by spirography, determination of a maximal inspiratory and expiratory flow-volume curve and, when possible, maximal static mouth pressures were determined. Peak inspiratory and expiratory flow, maximal expiratory flow at 50% and maximal static mouth pressures were significantly below normal values. Vital capacity, forced inspiratory volume in 1 s and the ratio of forced expiratory volume in 1 s and vital capacity were relatively normal. Nine patients had upper airway obstruction (UAO) as judged by abnormal values for peak inspiratory flow, the ratio of forced expiratory volume in 1 s and peak expiratory flow and the ratio of maximal expiratory and inspiratory flow at 50%. Flow-volume curves were normal in eight patients; four patients demonstrated flow decelerations and accelerations (type A) and 16 had a rounded off flow-volume curve (type B). Type A can be explained by UAO and type B by a combination of decreased effective muscle strength and possible UAO. Overall results of pulmonary function tests in patients without any clinical signs or symptoms of pulmonary disease point to subclinical upper airway obstruction and decreased effective muscle strength in a significant proportion of patients.

Visual contrast sensitivity in drug-induced Parkinsonism.

The influence of stimulus orientation on contrast sensitivity function was studied in 10 patients with drug-induced Parkinsonism. Nine of the 10 patients had at least one eye with contrast sensitivity deficit for vertical and/or horizontal stimuli. Only generalised contrast sensitivity loss, observed in two eyes, was stimulus orientation independent. All spatial frequency-selective contrast deficits in 15 eyes were orientation dependent. The striking similarity between the pattern of contrast sensitivity loss in drug-induced Parkinsonism and that in idiopathic Parkinson's disease, suggests that generalised dopaminergic deficiency, from whatever cause, affects visual function in an analogous way.

Disturbances of spatial perception in children.

Spatial perception was tested in 12 children with a localized brain lesion by means of the rod orientation test, line orientation test and facial recognition test. Only children with a lesion of the right hemisphere showed a disturbance of spatial perception.

Spatial disorientation in Parkinson's disease: no effect of levodopa substitution therapy.

In 22 patients with idiopathic Parkinson's disease, we tested spatial orientation with the rod orientation test, before and after levodopa substitution therapy was started. In both situations an impairment of spatial orientation could be demonstrated: levodopa did not improve this impairment.

Spatial contrast sensitivity in benign intracranial hypertension.

Spatial Contrast Sensitivity (CS) was studied in 20 patients with benign intracranial hypertension (BIH). At presentation CS loss was found in 43% of the eyes, and impairment of visual acuity attributed to BIH in only 16%. Nine patients had blurred vision or visual obscurations, all of whom had abnormal CS. The clinical application of CS measurement in BIH for monitoring the progression or regression of the disease is illustrated by serial measurements in 11 patients. Progressive visual loss in longstanding papilloedema and improvement of visual function in subsiding papilloedema can occur without any change in Snellen acuity or visual field charting.

Development of visual and tactile rod orientation in children.

Two groups of neurologically normal children (total number 64), aged from 4 to 13 years, were examined with the rod orientation test. In the second group, the line orientation test and finger tapping were also studied in addition to the rod orientation test. On the rod orientation test, the mean error rates decreased with age in both groups, and from the age of 10 the children performed as well as normal adults. In the period (ages 4-7 years) in which the greatest change in performance on the visual part of the rod orientation test had taken place (63%), a much smaller change occurred in the tapping frequency (23%). Thus the development of motor skills does not seem to be directly related to the development of spatial perception. The line orientation test did not show any developmental profile.

A case of organic brain syndrome following head injury successfully treated with carbamazepine.

A case of organic brain syndrome occurring in relation to psychological stress 2 years after a severe head injury is described. Treatment with haloperidol resulted only in slight improvement. A dramatic improvement was achieved with carbamazepine.

Effect of stimulus orientation on contrast sensitivity in Parkinson's disease.

We studied the effect of stimulus orientation on contrast sensitivity function in 21 patients with Parkinson's disease and in 10 normal subjects. This was done by measuring contrast sensitivity over a range of spatial frequencies for vertical and horizontal sine wave grating stimuli. There was a great test-retest consistency in normal subjects and patients. Fifteen of the 21 patients showed contrast sensitivity deficit in at least one eye. Orientation-specific loss was demonstrated in 17 of the 25 "affected" eyes. The most frequent type of orientation-specific loss was a notch defect, which preferentially affected the middle spatial frequencies. We attribute orientation-specific and spatial frequency-selective loss in Parkinson's disease to a functional disruption of neurons on the visual cortex.

Spatial contrast sensitivity in clinical neurology.

We studied contrast sensitivity function in normal subjects and in three illustrative cases with various neurological disorders. This was done by measuring contrast sensitivity over a range of spatial frequencies for vertical sinewave grating stimuli. It is demonstrated that contrast sensitivity function can give information about visual function not obtainable by conventional test procedures.