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On analysis of cerebrospinal fluid (CSF) samples from normal volunteer donors by high-resolution zone electrophoresis on agarose gel, an electrophoretically homogeneous protein band consistently appeared in the gamma-globulin region. Application of immunofixation electrophoresis in attempts to identify the band with use of monospecific antibodies against individual human serum proteins and against heavy- and light-chain immunoglobulins as well as polyvalent antisera did not produce a positive immunoprecipitation reaction with the protein band. The serum samples from these subjects did not show similar bands. Therefore, we conclude that this protein band is a normally occurring protein that is unique to CSF.

A novel dopamine agonist, which stimulates presynaptic dopamine receptors in the experimental animal, was administered acutely to four patients with chorea. Abnormal involuntary movements worsened, plasma prolactin levels fell, and plasma growth hormone concentrations increased in all patients tested. These effects resemble those associated with a postsynaptic rather than presynaptic dopamine agonist, and thus raise some question about the ability of conventional dopaminomimetic screens to predict clinical activity.

Buspirone is a novel anxiolytic whose pharmacological profile differs from that of the benzodiazepines and includes dopaminergic agonist effects. Because of these properties, buspirone's usefulness in the management of idiopathic Parkinson's disease was evaluated in a controlled study of 16 outpatients with stage I-IV disease. At doses of 10 to 60 mg/day, no significant group or individual effects could be discerned on standardized disability, dyskinesia, anxiety, or depression scales. At high dose levels (100 mg/day) however, there was a significant worsening of disability ratings and a decrease in dyskinesia scores; anxiety ratings were also significantly increased. The results indicate that buspirone is well tolerated by parkinsonian patients at conventional antianxiety doses of 10 to 40 mg. Clinical effects of high dose treatment, on the other hand, resemble those associated with a reduction in central dopamine mediated synaptic function. Since buspirone reportedly produces dose-dependent stimulation of norepinephrine containing neurons in the locus ceruleus and behavioral symptoms of such activation were observed, these clinical observations support the concept that central noradrenergic stimulation can adversely affect parkinsonian symptoms.

Neoplastic angioendotheliosis (NA) of the CNS is usually characterized by systemic vascular disease and a rapidly fatal course. We report a 52-year-old woman with dementia, spasticity, and sensory deficits developing insidiously over a year. Diagnostic findings included small CT lucencies in the brain and angiographic irregularities of medium-sized arteries (resembling cerebral arteritis). Brain biopsy revealed numerous small infarcts as well as pleomorphic, highly malignant tumor cells within cerebral meningeal vessels. Without treatment, she experienced only slight increase of dementia before death from pneumonia. At autopsy, there was almost complete regression of the intravascular cerebral tumor. The clinical course was unusual for the length of illness and the radiographic picture of cerebral vasculitis. Clinical features often present with NA--such as strokelike events, elevated sedimentation rate, renal impairment, and fever--were notably absent.

Seven dextral patients with Parkinson's disease (PD) who had predominant right-sided motor signs were compared on neuropsychological tests with eight dextral patients with PD who had predominant left-sided signs. Objective criteria for group designation were developed from clinical ratings. The patient subgroups were matched on age, education, estimated premorbid IQ, severity of motor signs, and medication usage. Patients with signs lateralized to the right were more impaired on tests of dominant hemisphere function (serial digit learning, confrontation naming, and verbal associative fluency), but no differences were found on tests of nondominant hemisphere function (form sequence learning, line orientation, facial recognition), indicating some correlation of neuropsychological performance with lateralization of predominant motor signs. Findings demonstrate that the cognitive deficits (particularly visuospatial) previously reported in the literature are not seen consistently in all subjects with PD.

The unloading reflex was tested on both sides of a patient with asymmetrical Parkinsonism. The motor activity after the silent period was significantly greater on the more affected side. The findings support the hypothesis that the response to unloading and the shortening reaction share a common mechanism which is exaggerated in Parkinsonism.

The pteridine cofactor of tyrosine and tryptophan hydroxylases, tetrahydrobiopterin (BH4), is concentrated in the striatum and other sites of brain monoamine synthesis and is a regulatory factor in the rate-limiting step of catecholamine synthesis. CSF content was decreased in eight patients with dystonic disorders (mean, 13.0 +/- 0.8 pmol/ml CSF compared with 20.6 +/- 1.4 in age-matched normals). We gave several trials of synthetic BH4 intravenously to 10 dystonic patients with benefit for 2 subjects with diurnally fluctuating dystonia, 1 with hemidystonia and parkinsonism, and 1 with generalized torsion dystonia. The findings of biopterin abnormality and the observed clinical improvements may point to a role for the cofactor in the pathogenesis and, possibly, the treatment of some forms of primary dystonia.

Based on an earlier study of EEGs and the present article on sensory evoked responses, with a total of 32 patients, it appears that routine electrophysiologic studies do not provide a good biological marker in Tourette Syndrome.

Electroencephalograms were obtained in 30 unmedicated, neurologically and intellectually intact Tourette syndrome (TS) patients, none having a history of clinically apparent seizure disorder. Six (20%) of initial 30 EEGs were judged to be abnormal, 2 (6.6%) on account of slowing of intrinsic rhythms and/or excess of slow frequencies and 4 (13.3%) on account of epileptiform alterations. Two of the latter 4 patients continued to show similar abnormalities in EEGs done 4 and 8 months later. Five of 6 patients with abnormal EEGs had history of migraine or migraine equivalents compared to 8 of 24 with normal EEGs (chi 2 = 4.88, P less than 0.05). It is concluded that in the population of Tourette patients studied, EEG abnormalities occurred in one-fifth of all patients despite an absence of medication effect, brain damage or seizure disorder and may, in part at least, be related to associated migrainous equivalents.

Twenty-four parkinsonian patients compared pergolide and bromocriptine therapy in a randomized double-blind, two-period crossover study. Both drugs were adjusted to an optimal balance between benefits and side effects. The mean daily dose and dose range for pergolide and bromocriptine were 3.3 mg (0.7 to 7.2) and 42.7 mg (5.8 to 87.5), respectively. Adjunctive medications, which for most patients included levodopa (plus carbidopa), were not altered during the study. A similar spectrum of clinical effects was found with both drugs and with lisuride, which was used to treat 13 of the patients in a previous study. Despite neurochemical differences in the antiparkinsonian ergots, their clinical utility is quite similar. We draw attention to hepatotoxicity and pleural reactions that may occur rarely with these drugs.

The effect of nadolol, a peripherally acting beta-adrenergic blocker, on resting tremor was examined in eight patients with idiopathic Parkinson's disease. With the use of a double-blind, placebo-controlled study of crossover design, patients received 80 to 320 mg of nadolol for 6 weeks while continuing their previous treatment regimen. Accelerometer readings showed a progressive reduction in tremor amplitude, but no change in tremor frequency, with increasing nadolol dosage. Maximum benefit was achieved at 240 mg, when resting tremor improved 50% (p less than 0.01). Physician ratings confirmed these findings. The results suggest that response to beta-adrenergic blockade may not be limited to postural or intention tremor and that such agents may not reliably differentiate between the tremor of Parkinson's disease and essential tremor.

Blink rate, a putative noninvasive marker of central dopamine activity, was assessed in medication-free patients with Parkinson's disease, progressive supranuclear palsy, Huntington's disease, and dystonia. The normal control rate of 24 blinks per minute was significantly higher than the rate of 12 and 4 blinks per minute recorded for patients with Parkinson's disease and progressive supranuclear palsy, respectively. The rates for patients with Huntington's disease and dystonia did not differ significantly from those of controls (36 and 26 blinks per minute, respectively).

It was predicted that tiaspirone, a novel compound, would benefit schizophrenic patients since in animal experiments it is a potent dopamine blocker. Following a placebo washout period of 1 to 2 weeks, 14 patients were treated for 28 days with the drug in a single-blind, dose ranging trial. GAS, NOSIE, and BPRS scores all showed significant improvement. No serious adverse effects were found. The absence of extrapyramidal symptoms was particularly encouraging since 10 of the 14 subjects had previously had them on other neuroleptics. Tiaspirone may represent a step forward in the search for a safer antipsychotic.

The authors studied CSF gamma-aminobutyric acid (GABA) in 14 Alzheimer patients and nine age-matched normal subjects. The five normal subjects who were wives of the demented patients had higher CSF GABA concentrations than the four normal subjects without demented spouses.

Stimulants, such as methylphenidate, are extensively used in the treatment of attention deficit disorder. In the present study, we used a double-blind placebo-controlled, prospective protocol to evaluate the effects of methylphenidate (MP) (dose 0.1 and 0.33 mg/kg three times daily) on the late event-related potentials, some of which are considered biological attention correlates. Sixteen patients, 6-15 years old, were tested, using an auditory target selection paradigm. The latencies of N200 and amplitudes of P150 increased with MP (p less than 0.01). These effects are in the direction of normal maturational change. The latencies of P300 tended to be shorter in adolescents than in children, and with high MP dose the P300 latencies became even shorter in adolescents but were prolonged in children (p less than 0.05). This pattern of change supports the view that pharmacological interactions with various cerebral phenomena including cognition may be age-specific.