Background: Increased levels of lactic dehydrogenase (LDH) in the cerebrospinal fluid (CSF) have been reported in association with several intracranial pathologies. No studies have been performed on patients with Guillain–Barré syndrome (GBS).
Aims: To study LDH isoenzymes in CSF of children with GBS.
Methods: CSF samples collected from nine patients with GBS were analysed for total LDH isoenzymes activity, and compared to samples from 15 patients with normal results.
Results: Mean total LDH activity was 33.33 (6.63) U/l. All patients had significantly increased LDH-3 isoenzyme compared to controls. LDH-3 was the predominant fraction, accounting for more than 50% of total LDH activity and present in more than twice the percentage of LDH-1 or LDH-2. By contrast, in the control group, there were high percentages of mainly LDH-1 and LDH-2.
Conclusions: GBS is apparently associated with a distinct LDH isoenzyme pattern in the CSF. More studies are needed to confirm the rise in LDH-3, as serial CSF analyses are unavailable, and to determine the optimum time of analysis when this finding first becomes detectable.
- lactic dehydrogenase isoenzyme
- Guillain-Barre syndrome
- cerebrospinal fluid
- CSF, cerebrospinal fluid
- GBS, Guillain-Barré syndrome
- LDH, lactic dehydrogenase
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Lactic dehydrogenase (LDH) is present in most tissues and body fluids examined, including cerebrospinal fluid (CSF). Studies have shown that patients with an intracranial pathology such as malignancy or bacterial infection have increased CSF LDH activity compared to healthy subjects (normal 40 U/ml).1–3
To the best of our knowledge, no reports have been published regarding CSF LDH activity in Guillain–Barré syndrome. In the present study we present nine children with a diagnosis of Guillain–Barré syndrome in whom the CSF showed a distinctive LDH isoenzyme pattern.
SUBJECTS AND METHODS
The study sample consisted of nine patients, aged 15 months to 9 years, with suspected Guillain–Barré syndrome, who underwent routine lumbar puncture at an inpatient department of our tertiary paediatric centre. The authors of this study did not participate in the clinical management of these patients. CSF analyses included total and differential cell counts, glucose and protein concentration, and cultures. None of the samples was bloody. One ml of CSF was stored at −20°C for later analysis of total LDH activity and LDH isoenzymes.
All patients fulfilled the clinical and laboratory diagnostic criteria for Guillain–Barré syndrome according to Asbury.4 Therefore, an increased protein concentration was required for diagnosis. The CSF LDH findings in the study patients were compared with those in 15 patients of mean age 10 (6.4) months who had undergone lumbar puncture during the same period because of suspected intracranial pathology with normal CSF findings. No relation between serum and spinal fluid activity has been noted; each varies independently of the other, presumably because of the blood–brain barrier.
Total LDH activity in the CSF samples was measured on a Hitachi-747 analyser (Boehringer-Mannheim) with an LDH kit (Boehringer-Mannheim) using the optimised standard methods. The LDH activity of spinal fluid appears to bear no direct relation to initial pressure, erythyrocyte count, protein, and sugar.1
Table 1 summarises the epidemiological and laboratory data of the patients. Besides the lumbar puncture, the laboratory results were within normal limits; serology and culture studies were negative for Campylobacter jejuni. In all nine patients, the CSF protein concentration was high (92–252 mg/dl) without pleocytosis (<6 WBC/mm3). Electromyography, performed in three of the nine patients, revealed evidence of acute denervation of muscle, with or without fibrillation.
Mean LDH activity in the CSF was 33.33 (6.63) U/l. In none of the patients was a value higher than 45 units detected, indicating that in all cases, total CSF LDH activity was within the normal range.
Table 2 presents the distribution of CSF LDH isoenzymes in the patients. This pattern is also illustrated in fig 1B. The same data for the control group are presented in table 2 and fig 1A. It is noteworthy that the control group samples showed elevations in LDH-1 and LDH-2 (p < 0.01) percentages and LDH-3 to a lesser extent. Only low percentages of LDH-4 and trace levels of LDH-5 were noted. By contrast, all patients with Guillain–Barré syndrome had notable increases of LDH-3 (p < 0.01). The LDH-3 isoenzyme was the predominant fraction, accounting for more than 50% of the total LDH activity and was present in more than twice the percentages of either LDH-1 or LDH-2.
To the best of our knowledge, this is the first report on the LDH isoenzyme pattern in the cerebrospinal fluid of patients with Guillain–Barré syndrome. In typical cases of Guillain–Barré syndrome, diagnosis is not difficult, though laboratory studies are often not helpful in the early stages of the disease. Prototypical laboratory results include albuminocytological dissociation in the CSF, and evidence of slowed nerve conduction on electrodiagnostic studies. However, the CSF protein level may not rise until a week after onset of symptoms, and the characteristic electrodiagnostic findings may not be evident until well after the clinical features are established.4 In these atypical cases, the analysis of LDH isoenzyme in CSF may serve as a useful, auxiliary tool for diagnosis. It is rapid, simple, and easily available, considering that all patients with suspected Guillain–Barré syndrome undergo lumbar puncture.
The most important finding of this study is the distinct pattern of isoenzyme distribution in Guillain–Barré syndrome in the presence of normal total CSF LDH activity. A comparison of figs 1A and B emphasises the clinical value of this finding. A predominance of LDH-3 activity, namely more than 50% of normal and/or twice that of either LDH-1 or LDH-2 accompanied by an acute progressive polyneuropathy is almost diagnostic of Guillain–Barré syndrome. The specificity of this finding in other clinical settings remains unclear.
Several conditions are known to modify the normal CSF LDH isoenzyme distribution, including bacterial meningitis (increase in LDH-4 and LDH-5), viral meningitis (increase in LDH-1 and LDH-2), intracranial tumours (LDH-5), cerebral haemorrhage (LDH-3, LDH-4, and LDH-5), leukaemic and lymphomatous infiltration (LDH-3 and LDH-4), and tuberculous meningitis (LDH-3).5,6
The origin of the increased LDH in the CSF of patients with a pathology of the central nervous system is not understood. Some authors have suggested a disturbance in the brain barrier which permits plasma LDH to reach the CSF, or LDH production by neoplastic tissue or white blood cells and exogenous bacterial sources.1,2,5,6 However, neither of these has yet been proven. The spinal fluid level varies independently of the plasma or serum activity.1
The present study suggests that LDH isoenzyme analysis may contribute to the diagnosis of the syndrome. More studies are needed to confirm the rise in LDH-3, as serial CSF analyses are unavailable, and to determine the optimum time of analysis when this finding first becomes detectable.
We thank Mrs Gloria Ganzach and Phyllis Curchack Kornspan for their editorial assistance, and Mrs Hana Fuchs from the Laboratory of Clinical Chemistry.
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