Cerebrospinal Fluid C-Reactive Protein in Parkinson's Disease: Associations with Motor and Non-motor Symptoms.

Parkinson' disease (PD) is characterized by motor symptoms including bradykinesia, resting tremor, postural instability, and rigidity and non-motor symptoms such as cognitive impairment, sleep disorder, and depression. Neuroinflammation has been recently implicated in pathophysiology of both motor and non-motor symptoms of PD. One of the most notable inflammatory proteins is C-reactive protein (CRP), which is elevated in the conditions of systemic inflammation. Using BioFIND database, we scrutinized the possible association between cerebrospinal fluid (CSF) levels of CRP and severity of PD motor and non-motor symptoms. Eighty-four healthy controls (HCs) and 109 PD subjects were entered into this study. A significant correlation was observed between CSF CRP levels and Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS part III) score and Montreal Cognitive Assessment (MoCA) score in PD patients. We found significant correlations between MoCA score and CSF CRP levels in female patients and between CSF CRP and MDS-UPDRS part III score and MoCA score in male patients. In linear regression, CSF CRP could predict 6.9 and 10% of changes in MDS-UPDRS part III score in all PD patients male PD patients, respectively. In summary, we confirmed that CSF concentrations of CRP are in correlation with motor and non-motor severity in PD subjects. Our findings suggest that neuroinflammation plays an important role in the initiation and probably progression of PD motor and non-motor symptoms, which may give us a better insight into the underlying pathologic mechanisms in PD.

Progressive encephalomyelitis with rigidity and myoclonus: the first pediatric case with glycine receptor antibodies.

IMPORTANCE: Progressive encephalomyelitis with rigidity and myoclonus is characterized by rigidity, painful muscle spasms, hyperekplexia, and brainstem signs. Recently, glycine receptor alpha 1 antibodies have been described in adult patients with progressive encephalomyelitis with rigidity and myoclonus. We describe a pediatric case. OBSERVATIONS: A 14-month-old child developed startle-induced episodes of generalized rigidity and myoclonus, axial hyperextension, and trismus, without impairment of consciousness. Episodes occurred during wakefulness and sleep, lasted seconds, and were accompanied by moaning, tachypnea, and oxygen desaturation. Imaging, cerebrospinal fluid, endocrine, metabolic, and genetic screening findings were normal or negative. She was treated with intravenous steroids and immunoglobulins with resolution of symptoms, but she relapsed weeks later. At this time, episodes were more severe. Glycine receptor alpha 1 antibodies were found in serum (titer of 1:200, later 1:320) and cerebrospinal fluid (titer of 1:2). Treatment was restarted with intravenous steroids and immunoglobulins, with major improvement, and she began treatment with oral steroids. She had 4 milder relapses, with improvement after treatment adjustments. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first pediatric case of progressive encephalomyelitis with rigidity and myoclonus associated with glycine receptor alpha 1 antibodies, a potentially severe but treatable antibody-mediated neurological disorder.

Biochemical alteration in cerebrospinal fluid precedes behavioral deficits in Parkinsonian rats induced by 6-hydroxydopamine.

BACKGROUND: Parkinson's disease, affecting at least 1% of population older than 65 years, is the most common neurodegenerative movement disorder. Up to now, no evidence has demonstrated that biochemical changes in CSF occur preceding the onset of Parkinson's symptoms. In this study, we tested the hypothesis that biochemical changes in CSF precede behavioral deficits in Parkinsonian animals. METHODS: We infused different doses of 6-OHDA into the MFB of rats bilaterally and examined the animals' movement behaviors, biochemical alterations in CSF, and dopaminergic neuronal number in the SNpc 1 week later. RESULTS: Our results indicated that animals with over 70% dopaminergic neuronal loss in the SNpc exhibited behavioral bradykinesia and rigidity, and a decrease of HVA in CSF. In contrast, animals with about 42% dopaminergic neuronal loss in the SNpc showed normal movement behaviors, but displayed a drastic decline of HVA in CSF. Furthermore, the number of dopaminergic neurons in the SNpc was positively correlated with the HVA level in CSF. CONCLUSIONS: Our findings demonstrate that biochemical alteration in CSF foreruns behavioral deficits and the HVA level in CSF is positively correlated with the number of dopaminergic neurons in the SNpc of Parkinsonian rats induced by 6-OHDA. Our results strongly suggest that additional studies are needed to evaluate usefulness of monitoring the HVA level in CSF for early detection of the loss of dopaminergic neurons in the SNpc that precedes the onset of Parkinsonian symptoms in humans.

Extrapyramidal signs in Alzheimer's disease: a 3-year follow-up study.

Occurrence of extrapyramidal signs was investigated in a follow-up study of 32 patients with probable Alzheimer's disease (AD). Bradykinesia and rigidity were observed in 39% and 11% of the neuroleptic-free patients at entry and in 72% and 61% at year 3, respectively. Tremor was not a predominant feature nor did its occurrence increase over time. Use of neuroleptics contributed to extrapyramidal signs; 75-100% of the neuroleptic-treated patients showed bradykinesia, rigidity or orofacial dyskinesia. The homovanillic acid (HVA) concentrations of the cerebrospinal fluid at entry were comparable to those of age-matched controls. Nor did HVA levels correlate with rigidity or bradykinesia in these early AD cases. Presence of bradykinesia or rigidity at the initial evaluation predicted more severe dementia and a poor prognosis over the period of 3 years, although interaction of initial clinical severity of dementia was significant. Of 15 patients with these signs 3 (20%) died and 8 (53%) needed institutional care, while of 17 patients without these signs only 1 (6%) died and 2 (12%) were institutionalized by year 3 (p less than 0.01).

Total biopterin levels in the ventricular CSF of patients with Parkinson's disease: a comparison between akineto-rigid and tremor types.

Total L-erythro-biopterin (T-BP) levels in the ventricular cerebrospinal fluid (CSF) were measured in 43 patients with Parkinson's disease (PD) and 12 age-matched neurological controls. In 5 of the PD patients and 1 control, lumbar CSF T-BP values were also measured. The mean ventricular CSF T-BP level in the PD patients, 15.6 +/- 0.5 pmol/ml (mean +/- SE), was significantly lower than that in the controls (21.3 +/- 1.4 pmol/ml, P less than 0.0001). The mean T-BP concentration in the ventricular CSF was 1.9 times higher than that in the lumbar CSF (P less than 0.0005), indicating a rostrocaudal gradient for the T-BP value in the CSF. When the PD patients were classified according to their predominant clinical features into 24 akineto-rigid (A-R) type and 19 tremor (T) type, there was a significant negative correlation between the T-BP levels and duration of illness only for the A-R type patients (rho = -0.605, P less than 0.005). No such significant correlation was found in the T type patients. These results may indicate a difference of pathophysiological changes in the brain between the 2 types of PD.

Cyclic nucleotides in cerebrospinal fluid of drug-free Parkinson patients.

Concentrations of cyclic nucleotides--adenosine-3',5'-monophosphate (c-AMP) and guanosine-3',5'-monophosphate (c-GMP)--were measured in cerebrospinal fluid (CSF) of 17 drug-free Parkinson patients and 12 controls. No significant difference between the cyclic nucleotide contents (p greater than 0.05) in CSF of patients and controls was detected, nor was there a correlation between the content and the degree of neurological disability. Besides, no changes in the cyclic nucleotide contents were detected in the subgroups of patients according to the prominence of tremor or rigidity/akinesia as the main symptoms of the disease.

Ventricular somatostatin-like immunoreactivity in patients with basal ganglia disease.

The concentrations of somatostatin-like immunoreactivity (SLI) in lateral ventricular fluid of patients with extrapyramidal motor disease were determined by specific radio-immunoassay. Mean SLI levels were significantly lower in patients with Parkinson's disease (mean +/- SEM); 42.9 +/- 2.9 fmol/ml) and in patients with dystonic syndromes (39.4 +/- 3.2) than in patients with benign essential tremor (65.3 +/- 9.7). The lowest levels were found in patients with athetosis (34.7 +/- 5.4). In parkinsonian patients somatostatin levels correlated with the degree of akinesia, rigidity and autonomic disturbances.

Stiff-man syndrome with abnormalities in CSF and computerized tomography findings. Report of a case.

We report a case of stiff-man syndrome with abnormal spinal fluid. Serum protein values were normal, but the spinal fluid levels of immunogammaglobulin G and acute-phase proteins were elevated. We discuss the possibility of an inflammatory process of the nervous system as a cause for these findings. Another interesting observation in our patient was that of local atrophies seen on computerized tomography, indicating hemispheral and especially brainstem lesions. Furthermore, as a new therapeutic possibility, we demonstrated the improvement of spasms and rigidity under the influence of heat.