CSF choline levels in groups of patients with cranial trauma or extrapyramidal disorders.

Choline levels in lumbar cerebrospinal fluid (CSF) were measured in patients with craniocerebral trauma (N = 67), Parkinson's disease (N = 20), miscellaneous extrapyramidal disorders (N = 28) and Huntington's chorea (N = 5). No differences in CSF choline levels were observed between these diagnostic groups and a group of neurological controls (N = 22). However, CSF choline levels were found to increase with age.     

Acetylcholine and choline in cerebrospinal fluid of patients with Parkinson''s disease and Huntington''s chorea.

Lumbar cerebrospinal fluid (CSF) acetylcholine (ACh) and choline (Ch) levels were measured in patients with Huntington's chorea (N=11), Parkinson's disease (N=8), and subjects at risk for Huntington's chorea (N=4), and all three groups were found not to differ significantly from normal controls (N=10). The values found for lumbar CSF ACh and Ch levels in the normal subjects were comparable with previously reported values. The use of physostigmine, a cholinesterase inhibitor, in collecting the CSF samples did not appear to make a difference with regard to ACh and Ch concentrations. Evidence suggesting a ventricular-lumbar gradient, with lumbar CSF Ch concentration being less than ventricular CSF Ch concentration, was found. Finally, ACh levels in CSF did not correlate with corresponding Ch levels.     

Cerebrospinal fluid GABA and homocarnosine concentrations in patients with Friedreich's ataxia, Parkinson's disease, and Huntington's chorea

Free and total gamma-aminobutyric acid (GABA) and homocarnosine concentrations were measured in the lumbar cerebrospinal fluid (CSF) of patients with Friedreich's ataxia, Huntington's chorea, and Parkinson's disease (with and without levodopa treatment), and compared with those determined in control subjects. Values found in Friedreich's ataxia or Parkinson's disease were not significantly different from those in controls. Unexpectedly, in Huntington patients, known to have a characteristic decrease in GABA concentrations in specific brain areas, CSF concentrations of total GABA and homocarnosine were significantly higher, whereas free GABA was not different from controls. These findings indicate that the measurement of CSF GABA and homocarnosine in patients with CNS degenerative diseases should be interpreted cautiously.     

The cerebrospinal fluid choline levels in patients with Huntington's chorea. Negative effect of haloperidol treatment.

Lumbar cerebrospinal fluid (CSF) choline (CH) levels were measured in patients with Huntington's chorea (n = 14). This group was found not to differ significantly from normal controls (n = 13). The values for lumbar CSF Ch levels in the normal subjects were comparable with previously reported values. Of the choreic patients, seven were put on haloperidol treatment (4--6 mg daily). The CSF choline level remained unchanged with this treatment after 20 days. CSF cholinesterase activity was measured in the control and choreic group. The results were not significantly different.     

Amine metabolites in the cerbrospinal fluid in Huntington''s chorea

The amine metabolites HVA and 5-HIAA in the lumbar CSF of 15 patients with Huntington's chorea were determined. A negative correlation was found between the severity of symptoms and the CSF HVA, but not 5-HIAA levels. The mean HVA concentration was lower than that of a group of patients with miscellaneous neurological disorders, similar to that of a group with miscellaneous psychiatric disorders and higher than that of a group with Parkinson's disease. The mean 5-HIAA concentration was similar to that of the neurological group and higher than those of the groups with psychiatric disorders or Parkinson's disease. CSF HVA and 5-HIAA concentrations of a single patient with severe akinetic rigid Huntington's chorea were similar to those found in Parkinson's disease. The findings are discussed in relation to previous neuropathological observations and to reported effects of drugs on the choreic symptoms.     

The cerebrospinal fluid choline levels in patients with Huntington's chorea

Summary Lumbar cerebrospinal fluid (CSF) choline (CH) levels were measured in patients with Huntington's chorea (n = 14). This group was found not to differ significantly from normal controls (n = 13). The values for lumbar CSF Ch levels in the normal subjects were comparable with previously reported values. Of the choreic patients, seven were put on haloperidol treatment (4–6 mg daily). The CSF choline level remained unchanged with this treatment after 20 days. CSF cholinesterase activity was measured in the control and choreic group. The results were not significantly different.     

Reduction of cerebrospinal fluid glutamic acid in huntington's chorea and in schizophrenic patients

Summary Glutamic acid levels were investigated in the cerebrospinal fluid and blood serum of patients with schizophrenia, Huntington's chorea, and sciatic nerve compression by lumbar disc protrusion. In the serum the glutamic acid levels were equal in all three groups; in the cerebrospinal fluid (CSF) of schizophrenic and Huntington's patients, however, the glutamic acid was decreased to almost half that of the lumbar disc group which served as control. Most of the patients were treated with neuroleptic drugs. However, since in one case (the daughter of a Huntington's patient) the CSF glutamic acid was decreased although this woman had had no neuroleptic treatment, it seems more likely that the glutamic acid decrease is due to the disease rather than to the neuroleptic treatment.Some of the Huntington's patients were under the care of Dr. K. Schröter, Dr. H. Pollok, and Dr. P. Rohrbach whose collaboration is gratefully acknowledged by the authors     

Cerebrospinal fluid levels of quinolinic acid in Huntington's disease and schizophrenia

The concentration of the endogenous excitotoxin quinolinic acid was determined in the cerebrospinal fluid of drug-free patients suffering from Huntington's disease or schizophrenia (control group). In both diseases, quinolinic acid concentrations were highly variable (less than 4-48 nM) but the mean levels for each disease group were not significantly different from each other or from the quinolinic acid concentration of normal cerebrospinal fluid. Analysis of steady-state cerebrospinal fluid quinolinic acid concentration is unlikely to be of value as a diagnostic tool in Huntington's disease.     

Beta-adrenergic receptor subtypes in the basal ganglia of patients with Huntington's chorea and Parkinson's disease.

The density of [125I]iodo-cyanopindolol binding to beta-1 and beta-2 adrenergic receptors was studied in post mortem basal ganglia samples of Huntington's chorea and Parkinson's disease patients using autoradiography. Whereas no significant changes were observed in sections from Parkinson's and Huntington's chorea grade 2 patients, a nearly complete loss of beta-1 binding sites was observed in the basal ganglia of Huntington patients at later stages of the disease. The concentration of beta-2 receptors was increased by a factor 2 in the posterior putamen of all choreic cases. These results are consistent with the view that beta-1 receptors are predominantly located on a subpopulation of neurons which degenerate at late stages of Huntington's chorea, while beta-2 receptors are present mainly on glial elements.     

Intravenous probenecid loading. Effects on plasma and cerebrospinal fluid probenecid levels and on monoamine metabolites in cerebrospinal fluid.

Probenecid blocks the active transport from cerebrospinal fluid to blood of homovanillic acid and 5-hydroxyindoleacetic acid, thus increasing cerebrospinal fluid levels of these products of central monoamine metabolism. The half-life in plasma of probenecid given as a single intravenous infusion (40 mg per kilogram of body weight) to patients with either Huntington's chorea or Parkinson's disease averaged about 6.6 hours. In cerebrospinal fluid, peak values for homovanillic acid and 5-hydroxyindoleactic acid occurred in samples collected 8 hours after the 1-hour probenecid infusion was started. Even after 4 hours, however, levels of both monoamine metabolites were significantly increased. There was a positive correlation between cerebrospinal fluid levels of probenecid and the increase in 5-hydroxyindoleacetic acid but not homovanillic acid. Compared with the oral administration of probenecid, the intravenous infusion technique produced more consistent elevations in plasma and cerebrospinal fluid probenecid levels, greater increases in cerebrospinal fluid homovanillic acid values, and fewer gastrointestinal side effects.     

Homovanilic acid in Huntington's disease and Sydenham's chorea.

Homovanilic acid (HVA) was determined in the lumbar CSF of 12 patients with Huntington's disease and 12 with Sydenham's chorea before and after probenecid administration. The means of HVA concentration (basal and after probenecid) were lower in those with Huntington's disease than in controls, and were even lower in a sub-group characterised by increased tone and slowness of voluntary movement. There was no correlation between CSF HVA values and the severity of abnormal movements, nor with length of the illness and age of the patients with Huntington's disease. The mean basal HVA concentration did not differ from controls in those with Sydenham's chorea but the accumulation with probenecid was significantly lower. These results suggest a decrease in cerebral dopamine release in both forms of chorea.     

A blinded study of the suppressibility of involuntary movements in Huntington's chorea, tardive dyskinesia, and L-dopa-induced chorea

Videotapes of patients with Huntington's chorea, tardive dyskinesia (TD), and L-DOPA-induced chorea in Parkinson's disease were taken while the patients were seated with their legs dangling. The videotapes were scored in a blinded fashion for suppressibility of dyskinesias. Most patients with TD or L-DOPA-induced chorea substantially suppressed their involuntary movements, whereas most patients with Huntington's chorea did not. There was a small overlap between the TD and Huntington's chorea groups and suppressibility therefore could not absolutely distinguish between them. Suppressibility testing may nonetheless be a valuable clinical tool since a good, excellent, or complete suppressibility rating was highly suggestive of TD but not Huntington's chorea. TD and L-DOPA-induced chorea may be more pathophysiologically similar to each other than either is to Huntington's chorea.     

Habituation of the orbicularis oculi reflex in dementia and dyskinetic states.

The habituation index is a quantitative expression of the ability of the orbicularis oculi (blink reflex) to adapt to a series of electrical stimuli applied to the supraorbital region. This parameter has been studied in a group of normal control subjects, and the results compared with those in cases of idiopathic and drug-induced Parkinsonism, states of dementia, and dyskinesias such as Huntington's chorea and senile chorea. Patients with Huntington's chorea showed a tendency for the reflex to habituate readily in contrast to patients with dementia caused by cortical atrophy and those with Parkinson's disease. Younger patients with Huntington's chorea had indices within the normal range. It seems unlikely that this test will prove of value in the detection of clinically unaffected relatives. Where dementia was associated with a reversible intracranial lesion, the habituation index was studied before and after treatment. Failure of habituation in this condition appears to be due to the release of a primitive protective reflex.     

CFS hydroxylase cofactor levels in some neurological diseases

The cerebrospinal fluid concentration of hydroxylase cofactor has been measured in patients with Parkinson's disease, the Shy-Drager and Steele-Richardson syndromes, adult onset focal dystonia, essential tremor, Huntington's disease and presenile dementia. The results were compared with age matched controls and low values were demonstrated for all disease groups studied except for focal dystonia.     

Ventriculo-lumbar gradient of concentration of total cerebrospinal fluid proteins: 1 - mechanisms of origin

In normal conditions there is a concentration gradient of proteins along the neuraxis. From a low level in the ventricles, ranging from 5 to 15 mg/10C ml, to an intermediate level in the cisterna magna, the protein content reaches its highest level in the lumbar sac, 12 to 44 mg/100 ml. Several mechanisms were considered to elucidate the origin of this gradient but many investigators think that the progressive increase of the protein concentration is best explained by the transfer of proteins from serum to the cerebrospinal fluid due to the relatively raised permeability of blood-cerebrospinal fluid barrier in the spinal subarachnoid space. This paper presents a study of the protein concentrations in cisternal and lumbar cerebrospinal fluid samples of patients with neurocysticercosis in activity. The 11 patients of the first group had free subarachnoid space communication between the cisterna magna and the lumbar sac; the 6 patients of the second group had a complete block of the subarachnoid space between these two levels. In every cerebrospinal fluid specimen the quantitative complement fixation test for cysticercus was performed and the titer determined in order to make an assessment of the central nervous system humoral immune response. The analysis of the data of this investigation shows that the concentration gradient of proteins is evident in the cerebrospinal fluid of patients with patency of the spinal subarachnoid space, and the ratio of concentrations of protein contents in simultaneous cisternal and lumbar samples was similar to that one observed in normal individuals. This gradient is also detected when the intensity of the humoral immune response is determined by quantitative complement fixation test for cysticercus in simultaneous cisternal and lumbar specimens. After the onset of spinal subarachnoid block, the confront of the results of the tests in cerebrospinal fluid samples, obtained before and after the blockage, shows a large increase both in the total protein content as well as the intensity of the humoral immune response, in the lumbar level. The similar increases both in protein concentration and titer of cysticercus complement fixation test in the lumbar fluid, in comparison with the cisternal fluid, in patients with patent spinal subarachnoid space, and the large simultaneous and similar increases in both protein content and titer of the cysticercus complement fixation test in the lumbar fluid of patients with spinal subarachnoid block are in disagreement with the usual explanation of the origin mechanisms of the gradient.(ABSTRACT TRUNCATED AT 400 WORDS)     

Indicators of brain biogenic amine metabolism in various extrapyramidal disorders

The authors describe the results of determinations of the main metabolites of dopamine (DA), serotonin (S) and noradrenaline (NA) in the cerebrospinal fluid (ventricular and lumbar) in patients with various extrapyramidal system diseases. A profound decrease was demonstrated in the concentration of homovanillic acid (HVA)--the end metabolite of DA in parkinsonism, reflecting damage to DA--containing pathways and reduced DA synthesis in basal ganglia. Treatment with L-DOPA raises considerably the HVA level in the cerebrospinal fluid evidencing increased DA metabolism in the brain during administration of its precursor L-DOPA. In torsion dystrophy a statistically significant difference was found in HVA concentrations in the ventricular fluid depending on the clinical manifestations of the disease. In the patients with local muscular rigidity HVA level was much lower than in patients with the hyperkinetic form of the disease. It is concluded that the character of changes in the cerebral dopaminergic systems differs phenotypically in the form of torsion dystonia. In hepatolenticular degeneration (Wilson's disease) the level of all studied metabolites was decreased, which could be an evidence of deficient cerebral metabolism of their precursors--amines. In cases of Huntington's chorea a low level of HVA was found in the ventricular fluid, reflecting decreased total amount of DA in the brain due to damage to the corresponding neurons. Absence of detectable changes in MHPG concentration (the main cerebral metabolite of NA) indicates that this amine plays a lower role than DA and S in the biochemical mechanisms of the pathogenesis of extrapyramidal motor disturbances. The obtained data are important for the understanding of the pathogenesis and for evolving therapeutic methods in extrapyramidal diseases.     

Cerebrospinal fluid choline levels are decreased in Parkinson's disease

We examined acetylcholinsterase (AChE) activity and choline levels in cerebrospinal fluid (CSF) in 16 patients with idiopathic Parkinson's disease and 9 control subjects of corresponding age: 8 were untreated Parkinson's patients; 4 were treated with carbidopa-levodopa (100/1,000 mg/day) for 20 +/- 3 months; and 4 were treated with carbidopa-levodopa (110/1,100 mg/day) for 28 +/- 18 months plus amantadine (200 mg/day) for 16 +/- 8 months. CSF choline levels (nmol/ml) were 2.97 +/- 0.79 (control subjects); 1.31 +/- 0.29 (untreated patients); 1.00 +/- 0.29 (carbidopa-levodopa treated); and 1.26 +/- 0.19 (carbidopa-levodopa/amantadine treated). Choline levels were significantly lower in untreated and treated patients compared to control subjects (p = 0.0001). AChE activity did not differ in Parkinson's disease patients as compared to control subjects. The reduced level of choline in CSF may reflect a deficit in choline transport into the brain or a decrease of choline-phospholipid output from the brain.     

Cerebrospinal fluid levels of diazepam-binding inhibitor in neurodegenerative disorders with dementia

We investigated CSF levels of diazepam-binding inhibitor (DBI), a recently discovered neuropeptide that allosterically modulates GABAergic transmission, in various neurodegenerative disorders with dementia (28 patients with Parkinson's disease, 10 with Alzheimer's disease, 7 with Huntington's chorea). We applied a battery of neuropsychological tests to determine the degree of dementia and to exclude the presence of mood alterations. CSF DBI levels were elevated in parkinsonian subjects with dementia and in patients with Alzheimer's disease, but decreased in Huntington's chorea patients. We hypothesize that modifications of CSF DBI levels may be related to a functional or structural alteration of the GABAergic system.     

Immunoreactive substance P and somatostatin in the cerebrospinal fluid of senile parkinsonian patients

The concentration of substance-P-like immunoreactivity (SPLI) and somatostatin-like immunoreactivity (SLI) in the lumbar spinal fluid of senile parkinsonian patients (mean age 77.6 +/- 6.7 years) and senile control patients (mean age 83.5 +/- 5.6 years) were determined by specific radioimmunoassays. Mean SPLI and SLI levels in the control group were 8.1 +/- 2.0 (SD) and 32.5 +/- 12.0 fmol/ml, respectively. The mean SPLI levels were not significantly different in the groups. The mean SLI level was significantly lower in the group of patients with Parkinson's disease (19.8 +/- 9.0 fmol/ml). A comparison with results in patients with senile dementia of Alzheimer type (SDAT) shows that, in addition to clinical and pathological correlations, Parkinson's disease of late onset may share a deficit in somatostatinergic neuromodulation with SDAT.     

Neurochemical alterations in Huntington's chorea: a study of post-mortem brain tissue

Dopamine, noradrenaline, glutamic acid decarboxylase and choline acetyltransferase were measured in various regions of brain obtained at autopsy from a large series of cases of Huntington's chorea, dying with advanced forms of the disease. Neurochemical values in the choreic cases were compared with those from control and schizophrenic cases. In brain tissue from choreic patients, highly significant increases in dopamine concentrations were found in the corpus striatum, nucleus accumbens and pars compacta of the substantia nigra. This is consistent with the hypothesis that the nigrostriatal dopamine system is spared and may exert a relatively unopposed action on striatal function. Noradrenaline concentrations were raised in the caudate nucleus, lateral pallidum and pars reticulata of the substantia nigra, indicating preservation of central noradrenergic pathways. Glutamic acid decarboxylase activity was reduced in all brain regions examined but, taking ante-mortem factors into account, the depletion was confined to the striatum and lateral pallidum. This is consistent with the view that striatal GABA-containing interneurons degenerate. Significant losses of choline acetyltransferase activity were observed in the striatum, nucleus accumbens, septal nuclei and hippocampus. The development of muscle rigidity in choreic patients did not significantly affect the neurochemical values. The neurochemical alterations in Huntington's chorea could not be attributed to differences in ante-mortem or post-mortem factors between the choreic group and the control and schizophrenic groups.