Low back pain scores correlate with the cytokine mRNA level in lumbar disc biopsies: a study of inflammatory markers in patients undergoing lumbar spinal fusion.

PURPOSE: The molecular mechanism behind pain in degenerative disc disease (DDD) and chronic low back pain (LBP) patients is largely unknown. This present study examines the association of LBP and disability to mediators of the inflammatory cascade, as indexed by mRNA gene expression of pro-inflammatory cytokine markers in the intervertebral disc (IVD). METHODS: Biopsies of the annulus fibrosus (AF) and the nucleus pulposes (NP) from patients with DDD undergoing 1-2 level fusion surgery at L4/L5 or L5/S1 were obtained from total of 34 patients [9 M, 25 F] with average age of 53 [32-63]. The mRNA expression of TNF-α, IL-1ß, and IL-6 in the AF and NP was analyzed using quantitative real-time polymerase chain reaction (RT-qPCR), and the expression level of these markers was correlated to the visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores (0-100) for pain and disability. RESULTS: We report a statistically significant positive correlation between pain intensity (VAS score) and the expression of TNF-α in both the AF (r = 0.54, p = 0.001) and NP (r = 0.40, p = 0.02), similarly with IL-1ß in AF (r = 0.37, p = 0.02) and IL-6 in NP (r = 0.40, p = 0.02). In addition, we found significant positive correlation observed between disability score (ODI) and expression of IL-6 in both AF (r = 0.36, p = 0.03) and NP (r = 0.41, p = 0.01). CONCLUSION: We conclude that the intensity of LBP and disability is associated with the level of inflammation in the disc.

Idiopathic normal-pressure hydrocephalus: clinical comorbidity correlated with cerebral biopsy findings and outcome of cerebrospinal fluid shunting.

OBJECTIVES: To elucidate the importance of clinically diagnosed cerebral comorbidity in idiopathic normal-pressure hydrocephalus (INPH) and its effect on improvement after shunt surgery as well as concordance with parenchymal pathological changes described in frontal cerebral biopsy specimens. METHODS: In 28 consecutive patients diagnosed with INPH and shunted according to clinical, radiological and cerebrospinal fluid dynamic criteria, concomitant disorders were carefully registered, with special emphasis on cerebrovascular disease (CVD) and possible Alzheimer's disease. During shunt surgery, a frontal cerebral biopsy specimen was obtained and subsequently analysed for pathological changes. RESULTS: One or several concurrent disorders were present in 89% of the patients, most often CVD (n = 17) and possible Alzheimer's disease (n = 12), of which eight patients presented both, diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. The shunt success rate was 33%. A clear tendency towards increasing prevalence of CVD or Alzheimer's disease was found in the subgroups with no improvement or clinical deterioration compared with the patients improving after shunt surgery. The presence of CVD tended towards an unfavourable shunt outcome. The pathological parenchymal changes reflected the clinical diagnoses of comorbidity, and were described in about half of the biopsy specimens, with Alzheimer's disease (n = 7) and vascular changes (n = 7) being the most common findings. However, no significant correlation was found with the clinical diagnoses of Alzheimer's disease and CVD. The presence of cerebral comorbidity, whether diagnosed clinically or by brain biopsy, did not preclude clinical improvement after shunt operation. CONCLUSIONS: A high prevalence of CVD and Alzheimer's disease was found in patients shunted for INPH, which was reflected, although less commonly, by similar neuropathological biopsy findings. No significant correlation was found between the presence of comorbidity and shunt outcome. The findings support the perception of INPH as a multiaetiological clinical entity, possibly overlapping pathophysiologically with CVD and Alzheimer's disease.

Lumbar elastance and resistance to CSF outflow correlated to patency of the cranial subarachnoid space and clinical outcome of endoscopic third ventriculostomy in obstructive hydrocephalus.

OBJECT: The purpose of the present study was to elucidate the value of the lumbar and intraventricular infusion tests in the selection of patients with obstructive hydrocephalus (OH) for endoscopic third ventriculostomy (ETV), and whether the presence of a diminished cranial subarachnoid space was a source of error in the interpretation of the results. METHODS: In 32 consecutive adult patients (15 M, 17 F, mean age: 46 years) with possible treatment-requiring OH, the resistance to cerebrospinal fluid (CSF) outflow (Rout) and elastance was measured with a lumbar infusion test. Eleven of the patients underwent an additional intraventricular infusion test. An ETV was subsequently performed in 20 patients, of whom 11 presented with idiopathic aqueductal stenosis and 9 with other various causes of OH. RESULTS: The presence of a diminished cranial SAS correlated significantly with increased lumbar elastance, but not with lumbar Rout. However, distinctly increased Rout values (>24 mmHg/mL/min, n=4) were only measured in the presence of a diminished cranial SAS. No significant correlation was demonstrated between the clinical outcome of ETV and lumbar elastance or lumbar Rout, although seven out of the eight improving patients with aqueductal stenosis presented normal lumbar Rout values. In patients undergoing both a lumbar and an intraventricular infusion test and improving after ETV (n=6), lumbar elastance was significantly increased compared to the intraventricular elastance. CONCLUSION: A diminished cranial SAS correlates with increased lumbar elastance and may explain the highly increased lumbar Rout values, possibly by impeding the bulk flow from the infusion. The majority of patients improving after ETV and presenting a normal sized cranial SAS presented normal lumbar Rout values. Supplementing the lumbar infusion test with an intraventricular test may help in predicting the outcome of ETV.

Intraventricular or lumbar infusion test in adult communicating hydrocephalus? Practical consequences and clinical outcome of shunt operation.

BACKGROUND: To investigate the therapeutic consequences of restricting the CSF dynamic evaluation to a lumbar infusion test (LIT), as opposed to our formerly applied intraventricular assessment (VIT), in patients with communicating hydrocephalus (CH). METHOD: All patients over 18 years of age referred with clinical and radiological indication of treatment-requiring secondary CH (n = 50) or idiopathic normal-pressure hydrocephalus (INPH, n = 33) were subjected to a LIT. Subsequently, a combination of the results of the LIT (mainly the resistance to CSF outflow) and the clinical presentation determined whether to proceed with (a) VIT before a decision about shunt surgery, (b) shunt surgery or (c) no further diagnostic investigation or surgery. FINDINGS: In 88 percent of the patients with secondary CH and 80 percent of the patients with INPH the decision on shunt surgery was made after performing exclusively a LIT. The shunting success rate was 90 percent in patients with secondary CH and 82 percent in patients with INPH, which however in the latter group decreased to 76 percent, when including the patients undergoing an additional VIT. The achieved shunt success rates are equal or better, compared to the results from previous studies using intraventricular assessment. CONCLUSIONS: LIT and VIT are equally reliable for selecting shunt responsive patients with CH, using clinical improvement rate as the main criterion for comparison. The practical and economic consequences are substantial: the LIT can be performed in an outpatient setting, whereas VIT necessitates hospitalisation for 1-2 days including occupation of the neurosurgical theatre and postoperative neuro-intensive monitoring.

Idiopathic normal-pressure hydrocephalus: evaluation and findings in a multidisciplinary memory clinic.

The diagnostic evaluation of patients with possible idiopathic normal-pressure hydrocephalus (INPH) is traditionally performed in the settings of either neurological, neurosurgical or psychiatric departments. The diagnostic procedure and findings in 71 consecutive patients referred with a clinical and radiological suspicion of INPH to our out-patient multidisciplinary memory clinic are evaluated. Primary diagnoses and potential concomitant disorders considered of secondary importance for the symptomatologies were established. Abnormal hydrodynamics, demonstrated by intraventricular pressure monitoring and infusion test were mandatory for the diagnosis of INPH. Mean age was 68 years and mean Mini-Mental State Examination (MMSE) score was 22. DSM IV criteria of dementia were fulfilled in 42%. In half of the referred patients (n=36), the suspicion of INPH was already disproved subsequently to the evaluation programme performed in the outpatient clinic. The main primary diagnosis was cerebrovascular disease (CVD) comprising 27% (n=19) of the referrals, whereas INPH was diagnosed in only 20% (n=14). Shunt improvement rate was 72%. The remaining patients were diagnosed as having one of 26 different conditions. A multiplicity of disorders mimics the INPH syndrome, with CVD being the primary differential diagnosis. Evaluating patients with possible INPH in an outpatient multidisciplinary memory clinic is an effective and rational diagnostic approach.