Abnormal glutamate metabolism in an adult-onset degenerative neurological disorder.

In patients with recessive, adult-onset olivopontocerebellar degeneration associated with a partial deficiency of glutamate dehydrogenase, the concentration of glutamate in plasma was significantly higher than that in controls. Plasma alpha-ketoglutarate was significantly lower. Oral administration of monosodium glutamate resulted in excessive accumulation of this amino acid in plasma and lack of increase in the ratio of plasma lactate to pyruvate in the glutamate dehydrogenase-deficient patients. Decreased glutamate catabolism may result in an excess of glutamate in the nervous system and cause neuronal degeneration.

Dyskinesias predict the onset of motor response fluctuations in patients with Parkinson's disease on L-dopa monotherapy.

The aim of the study was to investigate the relationship between dyskinesias and motor fluctuations in patients with Parkinson's disease on l-dopa monotherapy. We identified 116 patients on l-dopa monotherapy treated between 1965 and 1992 and followed until death. Dyskinesias occurred in 102 patients. Of these, 48 only developed dyskinesias while 54 had both dyskinesias and motor fluctuations. Among patients with both complications, 49 developed dyskinesias before fluctuations, and only five had dyskinesias after the onset of fluctuations. Our findings suggest that dyskinesias predict the onset of motor fluctuations, and may share a common pathophysiological mechanism.

Parkinson's disease: new approaches to diagnosis and treatment.

The findings three decades ago that the symptoms of Parkinson's disease were related to a deficiency of striatal dopamine and that they were reversible by the administration of levodopa heralded a new era of investigative interest in this disorder. Since then, there has been steady progress towards a better understanding of the nature of Parkinson's disease. The breadth of the clinical entity as regards its phenomenology and natural history have been more fully defined, new concepts regarding its etiology and early detection have been suggested and numerous approaches to treatment developed. In the main, therapy has been directed towards control of symptoms, but recent attempts at halting the inevitable progression have been developed. This presentation critically reviews these various aspects of Parkinson's disease.

Selegiline in the treatment of Parkinson's disease--long term experience.

L-deprenyl (selegiline) has been reported as a safe effective adjunctive agent to levodopa in the control of Parkinson's symptoms, as well as a means of preventing the progressive nature of the disease process. In an ongoing study, now in its 12th year, L-deprenyl has been administered 1. as monotherapy or 2. in combination with levodopa, to previously untreated patients in the early phases of the disease; 3. added to an existing regimen of levodopa when optimal therapeutic results are not being obtained. This report reviews our experience in each of these three treatment categories. Results obtained to date, indicate that L-deprenyl administered alone does not prevent the occurrence of signs of Parkinson's disease. Its administration with levodopa, as initial therapy, allows for use of lower dosage and less side-effects of the latter agent. When L-deprenyl is added to sub-optimal responders to levodopa, it attenuates fluctuating responses, particularly those of the 'end-of-dose' variety.

Treatment of Parkinson's disease in early and late phases. Use of pharmacological agents with special reference to deprenyl (selegiline).

There are at present numerous pharmacological agents available for the control of parkinson symptoms. None are ideal; all have their limitations. The most potent is levodopa administered with a peripheral decarboxylase inhibitor. However, because its effectiveness declines after long-term use and side effects increase in severity, it should be reserved for individuals with established symptoms which are functionally impairing. In patients with minimal symptoms, anticholinergic agents, or agents which facilitate dopaminergic mechanisms normally operative in the nervous system, should be used. In a limited trial, deprenyl has produced promising results during this phase of parkinsonism. Deprenyl's major usefulness however, has been demonstrated in patients under treatment with levodopa which has become complicated by fluctuating responses--particularly those of the end-start-dose variety. In such patients, it is possible to achieve an increase in "on" time and a decrease in the severity of parkinsonism. In most patients, such a response can maintained for a period of two years or longer.

Choreic movements induced by the use of methadone.

A 25-year-old man received methadone hydrochloride maintenance therapy for heroin addiction. Choreic movements involving the upper limbs, torso, and speech mechanisms developed. Discontinuation of methadone resulted in complete alleviation of the abnormal movements with no recurrence during the subsequent eight months. To our knowledge, this is the first recorded instance of a movement disorder induced by an opiate. The mechanisms by which drugs may after neurotransmitter relationships in the brain and produce symptoms of this type are discussed.

Acute autonomic neuropathy. Its occurrence in infectious mononucleosis.

A 13-year-old girl with acute onset of symptoms limited to autonomic dysfunction was found to be suffering from infectious mononucleosis. With symptomatic therapy, improvement gradually occurred over a period of seven months. The documentation of this case widens the spectrum of disorders to be considered as a cause of so-called acute pandysautonomia or autonomic neuropathy.

Meningoencephalopathy secondary to infectious mononucleosis. Unusual presentation with stupor and chorea.

We report a case of infectious mononucleosis in which central nervous system involvement was the presenting and sole manifestation of the disorder. The major symptomatology consisted of stupor, chorea, and signs of aseptic meningitis. We also discuss the clinical and laboratory features of the neurological manifestations of infectious mononucleosis and the theories as to its pathogenesis.

Striatal syndrome following hyponatremia and its rapid correction. A manifestation of extrapontine myelinolysis confirmed by magnetic resonance imaging.

Several pathologic reports have indicated the occurrence of extrapontine sites of myelinosis associated with electrolyte disturbance and its rapid correction. Clinical evidence of the presence of such lesions, however, have rarely been described. We report a case of a 50-year-old man who following rapid correction of electrolyte imbalance developed a profound striatal syndrome. The clinical manifestations, the course of his illness as well as response to therapy, confirmation of lesion sites by magnetic resonance imaging (MRI), and abnormalities on visually evoked potentials are described in detail.

Oculogyric crises and parkinsonism. A case of recent onset.

Oculogyric crisis in association with postencephalitic parkinsonism has been reported only following encephalitis lethargica (Economo's disease). Generally, it has been assumed that this phenomenon would fade away with the demise of these postencephalitic patients. Therefore, we report a case of recent onset of persistent oculogyric crisis with parkinsonism in a 35-year-old man following an apparent attack of encephalitis in 1972.

A case of sporadic juvenile Parkinson's disease.

Juvenile Parkinson's disease is rare. Virtually all reported cases are either associated with a family history or additional neurologic findings. We report a sporadic case of classic Parkinson's disease, without other abnormal neurologic signs and age at onset of 15 years.

Antibodies against arboviruses in postencephalitic and idiopathic Parkinson's disease.

Serum and CSF from patients with classic von Economo's postencephalitic Parkinson's disease, idiopathic Parkinson's disease and non-Parkinsonian neurological controls were tested for hemagglutination-inhibition antibodies to 17 arboviruses. All 35 CSF specimens from patients with idiopathic Parkinson's disease and controls were negative (ie, no inhibition of hemagglutination) with all the antigens. Of the total of 124 serums from the three study groups, 105 were also negative with all antigens tested. The only positive results were given by 19 serum specimens against one or more of group B arbovirus antigens, and/or against Batai and western equine encephalomyelitis antigens. There were no definitive differences in the distribution of these positive serum titers among controls, idiopathic Parkinson's, and postencephalitic Parkinson's cases. A causal relationship of the arboviruses tested with either the classical postencephalitic or idiopathic Parkinson's disease is not supported by the results of this study.

Early combination of selegiline and low-dose levodopa as initial symptomatic therapy in Parkinson's disease. Experience in 26 patients receiving combined therapy for 26 months.

Thirty-eight patients newly diagnosed as having Parkinson's disease (mean age, 57.3 years; mean Parkinson's disease duration, 2.7 years) in the earlier phase of the disease (mean Hoehn/Yahr stage, 2; mean motor scores, 11.4) were given selegiline (Deprenyl), 10 mg daily, and maintained on this drug alone until significant clinical worsening warranted the addition of low-dose levodopa (Sinemet, 25/100 three to four doses per day). Five of these patients were not yet receiving additional levodopa despite some worsening of motor scores. Of the 33 patients now taking combined therapy, seven have been followed up for 6 months or less. Twenty-four (92%) of the 26 patients taking combined therapy for a mean of 26 months (8.5 to 99 months) who have had Parkinson's disease for 6 years showed a dramatic improvement in their parkinsonism shortly after the addition of levodopa, with significant decreases in their rated motor scores, such improvement being maintained at their latest neurologic evaluation. Eighteen (75%) of these 24 patients responded to the combined selegiline/levodopa therapy with degrees of improvement equal to or greater than 50%, compared with their motor status at the start of combined therapy just before the addition of levodopa. This degree of "reversal" of parkinsonism on addition of levodopa (mean carbidopa/levodopa dose, 98/389 mg) was not observed in any of these same patients receiving selegiline alone for an average of 13.8 months. Four patients taking combined therapy developed mild, transient, abnormal involuntary movements, and end-of-dose pattern of response after more than 2 years of combined therapy (24.75 and 33.5 months, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

HLA-B14 antigen and postencephalitic Parkinson's disease. Their association in an American-Jewish ethnic group.

Eighteen unrelated American-Jewish patients of Eastern European extraction who had classical postencephalitic Parkinson's disease were typed for HLA-A, HLA-B, and HLA-C antigenic determinants. Compared with 147 ethnically matched controls, the HLA-B14 antigen showed a highly significantly increased frequency in the postencephalitic Parkinson's group (corrected P = .001). This association, though not necessarily reflecting genetic susceptibility to the disease, strongly suggests such a possibility in the pathogenesis of at least this particular variant of parkinsonism.

Protein-rich cytoplasmic bodies of substantia nigra and locus ceruleus. A comparative study in parkinsonian and normal brain.

A histochemical study of substantia nigra and locus ceruleus from postmortem brains showed the presence of small spherical cytoplasmic bodies stained selectively by the anionic phosphotungstic acid-hematoxylin (PTAH) stain at a pH of 2.5. The metachromatic reaction to PTAH indicates that these protein bodies contain a protein rich in free basic amino groups. The protein bodies are localized within the neuronal perikaryon as well as in their dendritic processes. These bodies abundantly present in the substantia nigra and locus ceruleus of normal brains were noticeably reduced or absent in parkinsonian brains. Lewy bodies when present show that their core gives the same metachromatic reaction to PTAH as do the protein bodies. These findings suggest that an abnormality of protein synthesis in the substantia nigra and locus ceruleus of parkinsonian brains may be related to the absence of protein bodies and the formation of Lewy bodies and play a role in pathogenesis of the parkinsonian state.

Quantitative cerebrospinal fluid IgG measurements as a marker of disease activity in multiple sclerosis.

The value of various parameters of reporting quantitative cerebrospinal fluid (CSF) IgG levels to indicate disease activity in 34 patients with clinically definite multiple sclerosis was examined. IgG alone correlated significantly with increasing degree of disability and increasing number of clinical central nervous system lesions. There was also a trend toward higher mean IgG levels when the course was relapsing and progressive as opposed to progressive or relapsing. For the IgG index, the relationships were the inverse of that noted with IgG alone. IgG-albumin ratio and IgG synthetic rate did not correlate significantly with course, number of CNS lesions, or degree of disability, and there was no statistically significant relationship between any parameter of reporting quantitative CSF IgG and age, duration of disease, history of recent exacerbation, or area of first involvement in the nervous system. We conclude that although newer methods of reporting CSF IgG elevations in multiple sclerosis are more sensitive and some of them, more specific, in confirming a diagnosis than CSF IgG alone, this parameter remains the best marker of disease activity in individual patients.

Quantitative CSF IgG measurements in multiple sclerosis and other neurologic diseases. An update.

To compare four ways of measuring CSF IgG levels in diagnosing multiple sclerosis (MS), we analyzed CSF samples of 106 patients with clinically definite, probable, or possible MS and 127 patients with other diseases. The IgG synthetic rate and IgG index were the most sensitive tests at 0.88 and 0.94, respectively; IgG alone and IgG-albumin ratio, at 0.53 and 0.59, were less valuable. The IgG synthetic rate (0.87) was more specific than the IgG index (0.73), making it the quantitative measure that best correlated with a clinical diagnosis of definite MS. However, combining these four methods showed an even higher correlation. Quantitative CSF IgG elevations occurred much less frequently in patients with clinically definite MS receiving immunosuppressives and in those with clinically probable and possible MS. We did not perform qualitative CSF IgG measurements, but our methods' sensitivity and specificity were comparable with those attributed to oligoclonal IgG bands by others. We also found numerous other diseases where elevations of CSF IgG occurred by all four methods.

Organic mental syndrome and confusional states in Parkinson's disease. Relationship to computerized tomographic signs of cerebral atrophy.

Ninety-three patients with a diagnosis of Parkinson's disease, otherwise unselected, were specifically evaluated for organic mental syndrome (OMS) and other neurologic motor signs other than those referrable to extrapyramidal dysfunction; in addition, they had cranial computerized tomography (CT) to measure any structural changes in brain parenchyma. Cortical (sulci) atrophy and ventricular enlargement as CT signs of cerebral atrophy were correlated with different clinical patterns of the disease. An age-adjusted control population, with intact mentation, was similarly studied. The presence of classic OMS in a sizable segment of the usual parkinsonian population was invariably associated with CT signs of cerebral atrophy. Atrophic changes on CT scans, however, were not necessarily correlated with any intellectual dysfunction, or only weakly so, independent of age. The "typical" parkinsonian patients without evidence of OMS were indistinguishable from an age-adjusted control group with regard to structural changes in their scans. However, the parkinsonian patients with definite, permanent OMS and other focal neurologic deficit probably constitute a separate or distinct subset of the parkinsonian population, with a pathologic substrate more likely to be similar to that of the so-called Alzheimer-type dementias. Duration of the parkinsonian syndrome was not predictive of either mental status or scan findings, after adjustment for age as a factor.

Subarachnoid hemorrhage secondary to spinal arteriovenous malformation and aneurysm. Report of a case and review of the literature.

A patient with recurrent subarachnoid hemorrhage was seen initially with intermittent signs and symptoms of intracranial and spinal cord dysfunction. Myelography and spinal angiography revealed an arteriovenous malformation (AVM) and aneurysm of the spinal cord. Extensive investigation failed to reveal any intracranial lesion. The relationship of subarachnoid hemorrhage at a spinal level to the development of remote neurological abnormalities is discussed, and previous reports of aneurysms associated with spinal AVM are reviewed.

Selegiline use to prevent progression of Parkinson's disease. Experience in 22 de novo patients.

To test the hypothesis that selegiline (L-deprenyl), a selective inhibitor of B-type monoamine oxidase, can halt the natural progression of Parkinson's disease, its use in 22 naive patients (mean age, 58 years; mean Parkinson's disease duration, 2.3 years) in the early stages (1 to 2) of the disease was studied. Patients were started and maintained on a daily dose of 10 mg of selegiline, and they underwent neurologic examinations at 3-month intervals using our center's disease staging and total rated disability scores. The criterion set for disease progression was defined as either the appearance of a new objective sign and/or a definite, persistent worsening (greater than 25%) of existing signs after the initiation of the selegiline trial. Patients remained on a regimen of selegiline [corrected] for periods ranging from 7 to 84 months. At the time of their latest neurologic examination, 17 (77%) of the 22 patients had conditions that demonstrably worsened with selegiline alone at an average of 10.8 months from the start of the drug therapy. Six of these 17 patients with worsening conditions (or 27% of the original 22) eventually required the addition of levodopa with carbidopa (Sinemet) on average at 13 months from the start of selegiline therapy; they have continued, to date, taking this combination for an additional mean follow-up period of 20.7 months. Four of the original 22 patients had relatively unchanged, stable neurologic status at the time of their latest examination (average follow-up period, 11.6 months).(ABSTRACT TRUNCATED AT 250 WORDS)