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.

Increasing incidence of childhood tumours of the central nervous system in Denmark, 1980-1996.

The registered incidence rate of childhood central nervous system (CNS) tumours has increased in several countries. It is uncertain whether these increases are biologically real or owing to improved diagnostic methods. We explored the medical records of 626 CNS tumours diagnosed in Danish children between 1980 and 1996. Population-based registers were used to extract data on mortality and background population. Temporal patterns were analysed by regression techniques. Most tumours were verified by computed tomography (78%) or magnetic resonance imaging (14%). Overall, the incidence rate increased by 2.9% per year (95% confidence interval (CI): 1.3;4.5) and the mortality rate increased by 1.4% per year (95% CI: -0.4;3.3). Among children aged 0-4 years, the survival rate after diagnosis remained almost unchanged, whereas among children aged 5-14 years, the 10-year survival rate improved from 59 to 74%. These data suggest that the incidence rate of CNS tumours among Danish children has truly increased, although alternative explanations cannot be excluded.

What is new about idiopathic intracranial hypertension? An updated review of mechanism and treatment.

Idiopathic intracranial hypertension (IIH) is the syndrome of raised intracranial pressure without clinical, laboratory or radiological evidence of intracranial pathology. IIH is a relatively rare disease but rapidly increasing incidence is reported due to a global increasing incidence of obesity. Disease course is generally said to be self-limiting within a few months. However, some patients experience a disabling condition of chronic severe headache and visual disturbances for years that limit their capacity to work. Permanent visual defects are serious and not infrequent complications. The pathophysiology of IIH is still not fully understood. Advances in neuroimaging techniques have facilitated the exclusion of associated conditions that may mimic IIH. No causal treatment is yet known for IIH and existing treatment is symptomatic and rarely sufficient. The aim of this review is to provide an updated overview of this potentially disabling disease which may show a future escalating incidence due to obesity. Theories of pathogenesis, diagnostic criteria and treatment strategies are discussed.

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.

Shunting to the sagittal sinus.

OBJECTIVES: To develop a shunt that drains CSF from the ventricles to the sagittal sinus under normal-physiological conditions. This shunting principle will not lead to any over-drainage, and a large proportion of the known shunt-complications will be avoided. METHODS: On the basis of the normal values for ICP, resistance to outflow and the production rate of CSF we have developed a shunt that drains CSF to the sagittal sinus and restores normal condition for the CSF dynamics. The shunt consists of two unidirectional valves, a pre-chamber, a resistance tube made of titanium, and a titanium tube leading CSF into the sagittal sinus. The shunt has been tested in 18 patients. Observation time ranged from 2 to 430 days, mean time 54 days. RESULTS: The first results from the use of the new shunt are very promising. It has an immediate effect on the clinical symptoms, it restores CSF dynamics (investigated with the shunt inserted) and the size of the ventricles is only gradually diminished. Slit ventricles have not yet been observed. In all patients the symptoms of hydrocephalus were relieved. No occlusion or thrombosis of the sagittal sinus have been observed. This is in agreement with the reports in the literature of shunting to the sagittal sinus, where 99 cases have been presented with an observation period of up to 6 years. The shunt has proven easy and safe to implant. CONCLUSIONS: Shunting to the sagittal sinus has proven easy and safe with regard to short term results. By using a dedicated shunt that drains at normal physiological parameters for the CSF dynamics any over-drainage is avoided, and it may be expected that the complication rate will be substantially smaller than with existing shunting systems.

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.

Thoracic disc herniation. Unilateral transpedicular approach in 35 consecutive patients.

BACKGROUND: Thoracic disc herniation is uncommon and surgery for thoracic disc herniation represents less than 1-2% of operations for disc disease. However, there is no consensus on the best approach and reports are based on small series. METHODS: A consecutive series of 35 thoracic disc herniations (25 in women and 10 in men) were treated between 1991 and 1996 using the transpedicular approach and followed in a prospective study. All patients had a preoperative MRI examination. The mean age was 51 years. The T6-7 and T7-8 level were the most frequent localization. The interval between onset of symptoms and operation ranged from 6 weeks to 4 years with a mean of 18 months. Presenting symptoms on admission was radiculopathy in 12 patients and myelopathy in 23 patients. Severe urinary symptoms were found in 2 patients, moderate symptoms in 9 patients, mild symptoms in 3 patients and 21 patient had no urinary symptoms. RESULTS: One patient was paraplegic immediately after surgery and she made no further improvement. A good result was found in 15 patients, a fair result was found in a further 11 patients but in 8 patients the outcome was unchanged with no effect of a reoperation in two cases. No clinical or radiographic features of instability were found. The postoperative course was uneventful, except in one patient with a wound abscess leading to discitis. CONCLUSIONS: The transpedicular approach can be an effective and safe method of surgical decompression in carefully selected patients.

Childhood medulloblastoma in Denmark 1960-1984. A population-based retrospective study.

Medulloblastoma is a common paediatric brain tumour, located in the cerebellum and in the IV ventricle, surpassed in frequency only by astrocytomas. 180 children below the age of 15 with a medulloblastoma of the posterior fossa were treated in Denmark in the 25-year period from 1960 to 1984 and followed up until the end of 1996, or until death. During the 25 years they accounted for 20% of all intracranial tumours in children in Denmark. All tumours were histologically verified. The mean annual incidence was 6.4x10(-6), decreasing slightly with a factor of 0.12x10(-6) per year. The male/female ratio was 2.1 - twice that of the background population of children (1.05). The 5-year survival rate following diagnosis, surgery and radiotherapy was 23%, and the 25-year survival rate was 16%. The 5-year survival rate was 8% in the first 5-year period of 1960-1964, increasing to 36% in the last period 1980-1984. Presumably the increase in survival depends on many factors, e.g. improved diagnostic methods and neuroanaesthesia, better operative technique (microscope), improvements in radiotherapy and the introduction of chemotherapy. The best predictive factors of a good prognosis were preoperative CSF shunting, radical tumour removal and complete radiotherapy, i.e. irradiation of the brain, tumour bed and spinal cord. The survival rate in the last five-year period was seven times higher than the survival rate found in a comparable Danish study from the years 1935-1959. Most of the children followed Collins law of risk index. The results of treatment in children with medulloblastoma remain unsatisfactory. Accordingly, participation in international prospective studies of multimodal treatment should be encouraged, possibly using chemotherapy prior to surgery.

Shunting effects in patients with idiopathic normal pressure hydrocephalus; correlation with cerebral and leptomeningeal biopsy findings.

Normal Pressure Hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space have been suggested as one of the patho-anatomical substrates. However, other types of adult onset dementia, predominantly Alzheimer's disease and Vascular Dementia, may mimic the clinical NPH characteristics. The purpose of the present study was to correlate cerebral parenchymal and leptomeningeal biopsy findings to the clinical outcome after CSF shunting in a prospective group of idiopathic NPH (INPH) patients. The study comprises 27 patients with INPH, diagnosed and shunted according to generally accepted clinical, imaging and hydrodynamic criteria. In all patients a frontal leptomeningeal and brain biopsy was obtained prior to the shunt insertion. Degenerative cerebral changes, most often Alzheimer (6 cases) or vascular changes (7 cases) were described in 14 out of 27 biopsies. Arachnoid fibrosis was found in 9 of the 18 biopsies containing arachnoid tissue. Overall, nine patients (33%) improved, of whom 6 presented Alzheimer or vascular changes in their biopsies. No correlation was found between clinical outcome and the presence or absence of degenerative cerebral changes and/or arachnoid fibrosis. However, a tendency towards higher improvement rates was noted in the subgroups presenting degenerative cerebral changes or arachnoid fibrosis. The results suggest that no constant morphological element exists in the syndrome of INPH. Various aetiologies may be involved in the pathogenesis and possibly in some cases co-existing: Patients may also improve by shunting despite the presence of degenerative cerebral parenchymal changes.

A comparison between ventriculo-peritoneal and ventriculo-atrial cerebrospinal fluid shunts in relation to rate of revision and durability.

Results of 884 first-time shunts inserted in the time period from 1958 to 1989 are retrospectively evaluated, 1) to perform a durability analysis of a shunt based on Kaplan-Meyer method, 2) to compare the rate of revision for ventriculo-atrial (VA) and ventriculo-peritoneal (VP) shunts, 3) to compare the durability of a VA shunt with a VP shunt and 4) to do a stratified durability analysis comparing the VA and VP shunts in relation to the following background variables: shunt type, time period and age of the patient. Furthermore the specific complications related to VA and VP shunts are identified based on findings in the literature. Overall one-year shunt durability is 57% and five-year shunt durability is 37%. The median shunt durability is 1.68 years. Revision rate is 51% for VA shunts and 38.5% for VP (p < 0.05). Shunt durability is longer for VP shunts though the difference is not significant (p < 0.1). By use of stratified analysis of shunt durability no differences however are found between the two shunting methods. Hence the apparent difference in revision rate between VA and VP shunts seems secondary to variations in follow-up time and variations in background variables. To supplement our statistical analysis we have performed a literature study to look at the specific complications associated with VA and VP shunts. It seems as if the specific complications in relation to the VA shunting method are more severe than in relation to the VP shunting method.

Epidemiology and prognosis in children treated for intracranial tumours in Denmark 1960-1984.

A total of 911 Danish children under 15 years of age were treated for an intracranial tumour in the 25-five year period 1960-1984. All cases were followed up to the end of 1994 or to emigration or death if one of these came sooner. The mean annual incidence was 32.5 per million children with a slight increase over the 25 years. The male/female ratio was 1.15 and close to the M/F ratio for the entire Danish population of children. Of the tumours, 46% were located in the supratentorial and 54% in the infratentorial compartment, and 94% were verified histologically. In order of frequency the most common types were astrocytomas (all grades, 35%), medulloblastomas (20%), ependymomas (14%), and craniopharyngiomas (5%). Total removal of the tumour was performed in 277 and partial removal, including biopsy, in 490 children. In 57 patients a shunt operation only was performed, and 87 children did not have an operation or died before the correct diagnosis was established. Radiotherapy was administered in 55%. The outcome depended on extent of removal, radiation, location and histology of the tumour. Most (784 or 86%) of the children survived more than 1 month after diagnosis or operation, and 353 children (39% of the whole series, 47% of those alive more than 1 month after diagnosis) were alive at follow-up. Of the survivors 29% had a tumour in the supratentorial midline, 26% one in the lateral part of the supratentorial area, 31% a cerebellar tumour and 13% a IV ventricle tumour. It was possible for 66% of the survivors with supratentorial and 90% of those with infratentorial tumours to lead a normal life. The long-term prognosis was especially good for children with cerebellar and supratentorial astrocytomas and optic chiasma tumours. Children with juvenile cerebellar astrocytoma had the best prognosis: 90% were alive at the end of the follow-up period, as against 20% of those with medulloblastoma and 6% of those with glioblastoma. A comparison of the data from the present series and from a similar Danish series of intracranial tumours in 533 children seen in the years 1935-1959 shows no significant differences in location or histology, a slight increase in annual incidence, and improved survival rates during the 50 years in question.

Age dependency of resistance to cerebrospinal fluid outflow.

OBJECT: Resistance to cerebrospinal fluid (CSF) outflow (Rout)is an important parameter in assessing the need for CSF shunt placement in patients with hydrocephalus. The normal lower limit of Rout has been estimated on the basis of the clinical effect of shunt placement in patients with varying values of Rout and in young healthy volunteers. The lack of clinical effect from CSF shunts in some elderly patients, despite elevated Rout,suggests that the normal value of Rout increases with age and may be higher in elderly persons. The aim of the present study was to examine the relationship between Rout and age in patients without known CSF dynamic disturbances. METHOD: Fifty-two patients ranging from 20 to 88 years of age and with no known CSF dynamic disorders were examined. The Rout was measured using a lumbar computerized infusion test. The correlation between Rout and age was analyzed by performing linear regression. The Rout increased significantly with patient age. The Rout in a patient in the eighth decade will be approximately 5 mm Hg/ml/minute higher than in a young patient. CONCLUSIONS: The present study shows a small but critical increase in Rout with increased patient age. A notable residual variation was present and borderline values of Rout should be regarded and used with caution.

[Frequency of infections after shunting of hydrocephalus. An analysis of 884 shunts]. / Infektionsfrekvens ved ventilbehandling af hydrocephalus. En opgørelse af 884 ventiler.

Postoperative infections are major complications to cerebrospinal fluid (CSF) shunting in the treatment of hydrocephalus and other conditions with impeded CSF transportation. In a retrospective study 884 first-time shunts inserted in the years 1958-1989 are investigated. Infection rate is studied including influence of following variables: time period, age of patient, education of neurosurgeon, length and time of operation and placement of the distal drain. Overall infection rate for all implanted CSF shunts is 7.4% (5.7-9.3%) and acute rate of infection is 6.2% (4.6-7.9%). Rate of infection is virtually constant for all variables except education of the neurosurgeon. Neurosurgical trainees have significantly higher infection rates. Use of prophylactic antibiotics is still controversial No prospective, double blinded studies including sufficient number of patients to evaluate this issue exist today. Meta-analysis studies conclude that use of prophylactic antibiotics is associated with a significant reduction in subsequent CSF shunt infection. We recommend that shunt implantation primarily be performed by highly trained neurosurgeons and that there should be increased supervision during CSF shunt operations performed by neurosurgical trainees.

Frontal brain and leptomeningeal biopsy specimens correlated with cerebrospinal fluid outflow resistance and B-wave activity in patients suspected of normal-pressure hydrocephalus.

OBJECTIVE: Normal-pressure hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space has been suggested as the pathoanatomic basis. The purpose of the present study was to investigate whether meningeal fibrosis causes increased resistance to cerebrospinal fluid outflow (R(out)) and/or increased B-wave activity and whether pathological changes in the brain parenchyma after brain compliance, causing increased B-wave activity. METHODS: The study involved a group of 38 consecutively studied patients with clinical and radiological evidence of idiopathic NPH, for whom a frontal brain biopsy was obtained. For 29 patients, hydrodynamic criteria of NPH were fulfilled and a ventriculoperitoneal shunt was performed. RESULTS: Meningeal fibrosis was found in 12 of 25 biopsies containing arachnoid tissue, but no correlation with R(out) or B-waves was found. Pathological parenchymal changes, most often Alzheimer's disease (10 cases) or vascular changes (10 cases), were found in 21 biopsies, but no correlation with B-waves or R(out) was found. CONCLUSION: The results suggest that leptomeningeal fibrosis is not the only pathoanatomic basis of increased R(out) and/or B-wave activity in patients with NPH and that various degenerative changes in the parenchyma may be responsible for the altered cerebrospinal fluid dynamics characteristic of NPH.

How many neurosurgeons do we want to educate in Europe annually? The Danish proposal.

The neurosurgical population consists of professors, consultants, specialised senior registrars, and doctors in training (senior registrars, trainees and young doctors to be educated as neurosurgeons). Knowing number and size of the neurosurgical departments in each European country, the number of staff members, the politics of retirement (age, educational level) and the age of every neurosurgeon it is possible to calculate the exact number of trainees needed per year to maintain a state of balance in every single European country. With Denmark as a model we based our assessments partly on a simple calculation model of the exact annual number of neurosurgical trainees or senior registrars and partly used an actuary flow model for calculation. In Denmark with 5 neurosurgical departments, 5.2 mill. population and a retirement age of 70, we have an average of 1-2 newcomers per year and maintain a bulk of 10 senior registrars in education. Thus there will be a balance between intake of newcomers and retirement, of course with some unknown factors as unforeseen dismissal or resignation, death rate among neurosurgeons and transfer to private practice.

Prognostic factors in oligodendrogliomas.

An outcome analysis was performed on 96 patients with pure cerebral oligodendrogliomas operated in the 30-year period 1962 to 1991. The most important predictive prognostic factors were youth and no neurological deficit, demonstrated as a median survival for the group younger than 20 years of 17.5 years and for the group older than 60 years of 13 months. The group without neurological deficits had a 5-years survival of 43 per cent while the group with deficits had a 5-years survival of 5 per cent. The 5-years survival for oligodendroglioma of grade II was 46 per cent and for grade III 10 per cent. We found no effect of radiotherapy on survival, neither in the whole material or in any subgroup.