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.

Endocrine studies in patients with pseudotumor cerebri. Estrogen levels in blood and cerebrospinal fluid.

In 15 patients fulfilling conventional diagnostic criteria for pseudotumor cerebri, anterior and posterior pituitary functions were examined. Eight of 12 female patients with pseudotumor were grossly overweight. Except for a subnormal response of growth hormone level to insulin-induced hypoglycemia in four patients, no major disturbances were found in pituitary, gonadal, thyroid, or adrenal functions. Vasopressin concentration in the cerebrospinal fluid was increased in patients with pseudotumor, whereas cerebrospinal fluid concentration of estrogens was below detection limit.

Motor disturbances in normal-pressure hydrocephalus. Special reference to stance and gait.

Motor disturbances in 16 patients with normal-pressure hydrocephalus were assessed by quantitative registration of handwriting, fine movements of the hand, hand tremor, postural instability, and gait. Tremor intensity was measured using an accelerometer and electronic integration of the accelerometer curves. Postural instability was measured on a computer-assisted force-plate, and computerized analysis of gait was made using an instrumented treadmill. Severe disturbances in motor performance in the upper extremities and postural stability were found. The gait of the hydrocephalic patients was characterized by a very low speed, short steps, ataxia (especially in the vertical direction), and high energy consumption. After shunt operation, significant improvement was found in motor performance in the upper extremities and postural stability, and gait ataxia decreased in all patients to values within the 95% confidence interval of age-matched controls.

Visual evoked potentials in pseudotumor cerebri.

Pattern reversal visual evoked potentials in 13 patients with pseudotumor cerebri were significantly delayed (99 +/- 7.3 ms [mean +/- SD]) compared with the findings in 20 normal subjects (94 +/- 2.7 ms), although only four patients had latencies outside the normal range. There was, however, a significant correlation between the intracranial pressure and the latency of visual evoked potentials. After medical treatment of the intracranial hypertension, visual evoked potential latencies decreased in patients who recovered and in whom the papilledema disappeared. In one patient with progressive visual failure, the visual evoked potentials were abnormal before disturbances of visual fields and visual acuity were evident. Repeated examinations of visual evoked potentials might be of value in patients with pseudotumor cerebri to ensure neurosurgical intervention in due time to prevent visual loss in patients with impending optic nerve atrophy.

24-hour cerebrospinal fluid levels of vasopressin in hydrocephalic patients.

The variation in vasopressin concentrations of ventricular cerebrospinal fluid and plasma throughout a 24-h period was studied in 10 patients with hydrocephalus. In 6 control patients, the diurnal variation in plasma vasopressin concentrations was studied. Vasopressin concentrations were determined by radioimmunoassay in plasma and in extracted and unextracted cerebrospinal fluid. Cortisol and osmolality in plasma were also measured. Vasopressin concentrations measured in extracted cerebrospinal fluid showed only small intra- and interindividual variation, while the corresponding values for unextracted cerebrospinal fluid were 2-5-fold higher and showed more variation. Plasma vasopressin concentrations varied considerably throughout the 24-h period in the individual hydrocephalic patient and between the patients. The pattern of variation was inconstant with no circadian rhythm, and the variation was not related to any changes in plasma osmolality, blood pressure or intracranial pressure. In some of the patients, the normal diurnal pattern of variation in plasma cortisol was broken, however, without a relation to the observed fluctuations in vasopressin concentrations. The abnormal variation of plasma vasopressin and cortisol was considered to reflect stress in connection with the intracranial pressure monitoring procedure. In the control patients, plasma vasopressin showed only small variations and plasma cortisol showed a normal diurnal rhythm. It is concluded that cerebrospinal fluid vasopressin concentration in patients with hydrocephalus is very constant throughout the day, even when plasma vasopressin concentrations show marked episodic increases. Thus, a circadian rhythm in the cerebrospinal fluid vasopressin concentration, as reported in several animal species, could not be confirmed in these patients.

Increased brain water self-diffusion in patients with idiopathic intracranial hypertension.

PURPOSE: To investigate changes in brain water diffusion in patients with idiopathic intracranial hypertension. METHODS: A motion-compensated MR pulse sequence was used to create diffusion maps of the apparent diffusion coefficient (ADC) in 12 patients fulfilling conventional diagnostic criteria for idiopathic intracranial hypertension and in 12 healthy volunteers. RESULTS: A significantly larger ADC was found within subcortical white matter in the patient group (mean, 1.16 x 10(-9) m2/s) than in the control group (mean, 0.75 x 10(-9) m2/s), whereas no significant differences were found within cortical gray matter, the basal nuclei, the internal capsule, or the corpus callosum. Four of 7 patients with increased ADC in subcortical white matter also had increased ADC within gray matter. CONCLUSION: Measurement of diffusion coefficients in vivo demonstrated increased local water mobility within subcortical white matter in 7 patients with idiopathic intracranial hypertension that otherwise appeared normal on conventional MR imaging. Further studies are necessary to assess the clinical significance of these observations.

High cerebrospinal fluid concentration of glial fibrillary acidic protein (GFAP) in patients with normal pressure hydrocephalus.

The concentration of glial fibrillary acidic protein (GFAP) in lumbar cerebrospinal fluid (CSF) was measured in 12 patients with normal pressure hydrocephalus (NPH) 11 patients with primary degenerative dementia (PDD), 8 patients with various other neurological diseases, and 18 patients without signs of organic nervous disease (controls). Mean CSF GFAP concentration was significantly higher in NPH patients: 96 +/- 23 ng/ml (SEM) when compared with PDD patients: 8.2 +/- 1.9 ng/ml (P less than 0.01), or with controls: 4.3 +/- 0.7 ng/ml (P less than 0.01). Only 2 NPH patients had a GFAP concentration within the range of the control group (2-14 ng GFAP/ml CSF). No significant differences were found between the PDD patients and the control group, or between the group of patients with other neurological diseases and the control group. In addition, a rostro-caudal gradient of GFAP in CSF could be demonstrated. In 6 NPH and 2 PDD patients both ventricular and lumbar CSF samples were investigated. In all cases the ventricular GFAP concentration was higher than the lumbar concentration. The difference was statistically significant (P less than 0.01). Our results suggest that determination of CSF GFAP concentration might be of diagnostic value in discrimination between NPH patients and patients with enlarged ventricles associated with degenerative brain disease.

Low cerebrospinal fluid concentration of brain-specific protein D2 in patients with normal pressure hydrocephalus.

The synaptic membrane glycoprotein D2 was measured in cerebrospinal fluid (CSF) and plasma in 13 patients with normal pressure hydrocephalus (NPH), in 14 patients with primary degenerative dementia of Alzheimer type (PDD), and in 24 patients without evidence of organic nervous disease (controls). Mean CSF D2 concentration was significantly lower in NPH patients: 299 +/- 48 ng/ml (SEM) (P less than 0.001) than in PDD patients: 658 +/- 50 ng/ml (SEM) and in controls 641 +/- 45 ng/ml (SEM). Plasma D2 concentrations were higher in PDD patients compared with those found in controls. Determination of CSF D2 concentrations might be of diagnostic value in discrimination between patients with NPH and PDD patients with enlarged ventricles associated with diffuse brain atrophy.

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.

Antibiotic prophylaxis in cerebrospinal fluid shunting: a prospective randomized trial in 152 hydrocephalic patients.

The authors report a prospective, randomized 18-month study on the effect of prophylactic antibiotic treatment in 152 hydrocephalic patients in whom clean shunt operations or revisions were done. The treated group received methicillin (totally 200 mg/kg) divided into six i.v. doses during 24 hours starting at the induction of anesthesia. Patients allergic to penicillin received erythromycin instead. Seventy-nine patients received antibiotics, and 73 (the control group) received none. All patients were followed at least 6 months after operation or to their death. Eleven patients developed signs of infection, giving an overall infection rate of 7.2%; however, the infection occurred less than 1 month after the operation in only half of these. Six of the patients had septicemia, 4 had peritonitis, and 1 had meningitis. In the treated group, the infection rate was 8.9%; in the control group, the rate was 5.5%. There was no statistically significant difference. The prophylactic antibiotic regimen in this investigation did not reduce the infection rate connected with cerebrospinal fluid shunting procedures.

Long-term follow-up review of patients with acute and subacute subdural hematomas.

The authors present 149 patients suffering from acute (112) and subacute (37) subdural hematomas admitted during the 10-year period 1965 to 1974, with a follow-up period of 2 to 12 years. During the time of observation, 104 patients died and 45 survived; 73% of the patients with acute and 27% with subacute subdural hematomas died. Of the patients with an acute subdural hematoma, 11% went back to work, as against 32% of those with subacute subdural hematomas. The 5-year survival rate was 28% in patients with acute and 76% in patients with subacute subdural hematomas.

Long-term prognosis in children with benign cerebellar astrocytoma.

In 44 children with benign cerebellar astrocytoma, operated on between 1935 and 1959, two histological types could be distinguished, namely, a so-called juvenile type (31 children) and a diffuse type (13 children). All the children were followed to April, 1976, and the histological review was performed without knowledge of the survival in the single patient. For children with the juvenile type of cerebellar astrocytoma the 25-year cumulative survival rate was 94%, as against 38% for children with the diffuse type. It has thus been demonstrated that the morphological difference between the two types corresponds to a marked difference in survival rate.

Relationships between intracranial pressure, ventricular size, and resistance to CSF outflow.

In 230 patients with normal-pressure hydrocephalus, high-pressure hydrocephalus, or benign intracranial hypertension, measurements of the intracranial pressure (ICP), ventricular size, and cerebrospinal fluid (CSF) outflow resistance (Ro) have revealed a linear relationship between ICP and Ro. It is shown that on average the CSF formation rate tends to decrease with increasing ICP. It is also shown that the size of the ventricles increases as the ICP levels off toward normal values. The clinical implication of this is that a small or normal ventricular size in acute or subacute phases does not preclude defective CSF resorption.

Intracranial pressure and conductance to outflow of cerebrospinal fluid in normal-pressure hydrocephalus.

Forty patients with clinical evidence of normal-pressure hydrocephalus were studied by monitoring intraventricular pressure during a 24-hour period, and by a lumboventricular perfusion test for measurement of the conductance to outflow of cerebrospinal fluid (CSF). The purpose of the study was to investigate whether there is a relationship between intraventricular pressure and conductance to outflow of CSF, and whether it is possible to use the results from pressure monitoring in the selection of patients who may be expected to benefit from shunting therapy. The conductance to outflow was used as an evaluation factor in the selection of patients to be treated by a shunt. The conductance to CSF outflow differed by twelvefold between the lowest and highest values. The level of resting intraventricular pressure was within normal limits in all patients. Accordingly, there was no evidence of a relationship between conductance to outflow and intraventricular pressure. So-called B-waves were seen more frequently in patients with decreased conductance to outflow, but were also present in patients with high conductance to outflow. Therefore, the presence of B-waves does not imply a low conductance to outflow of CSF.

Cerebrospinal fluid conductance and compliance of the craniospinal space in normal-pressure hydrocephalus. A comparison between two methods for measuring conductance to outflow.

Conductance to outflow of cerebrospinal fluid (CSF) has been measured by both a lumboventricular perfusion and a bolus injection method in 24 patients with normal-pressure hydrocephalus. One purpose was to investigate whether the less time-consuming technique of bolus, injection gave results comparable to the results obtained by the lumboventricular perfusion technique. There was a poor correlation between the results obtained by the two measurements of conductance to outflow of CSF. It is concluded that the bolus-injection technique cannot substitute for the lumboventricular perfusion test. Compliance of the CSF space was measured by the bolus injection. The presence of B-waves, recorded from long-term intraventricular pressure monitoring, could be correlated to the sum of conductance to outflow and compliance. The correlation offers a possible explanation of the nature of B-waves.

Cerebral blood flow in patients with normal-pressure hydrocephalus before and after shunting.

Cerebral blood flow (CBF) was measured by xenon-133 inhalation and single photon emission tomography in 17 demented patients with normal-pressure hydrocephalus before and after shunt treatment. All patients had a decreased conductance to outflow (C out) of cerebrospinal fluid as measured by lumboventricular perfusion (C out less than 0.12 ml X mm Hg-1 X min-1). Computerized tomography (CT) scanning, clinical assessment, and neuropsychological grading were performed pre- and postoperatively. The preoperative CBF studies revealed abnormal flow patterns in all patients. Fourteen patients showed moderate-sized, large, or very large central low-flow areas, and four patients had reduced flow bilaterally in the occipital and contiguous temporoparietal regions. After shunting, six patients had a significant reduction in the size of the central low-flow area on the CBF map, agreeing well with the changes of ventricular size on the CT scan. All six patients showed an improvement in either clinical or neuropsychological grading. In 10 of the remaining 11 patients flow patterns were essentially unchanged; one patient deteriorated further. Four of these 11 patients improved on postoperative clinical or neuropsychological testing. Thus, a positive correlation was found between the changes in CBF and the reduction of the ventricular size on the CT scan, but changes in CBF as measured by the present technique did not accompany improvement in the functional state in all patients.

Intracranial pressure and cerebrospinal fluid outflow conductance in healthy subjects.

Conductance of cerebrospinal fluid (CSF) outflow (Cout) is an important parameter to be considered in patients with CSF circulation abnormalities. In patients with normal-pressure hydrocephalus it is the single most important parameter in determining if the patient needs CSF shunting. The lower normal limit for Cout has been estimated from the effect of shunting in patients with normal-pressure hydrocephalus, from patients retrospectively reevaluated after recovering from illness, and from patients with known abnormalities in the brain or the CSF system. The true value of Cout in normal individuals, however, has hitherto not been reported. In the present study, Cout has been measured by a lumbar infusion test in eight young volunteers with no suspicion of disease. The mean intracranial pressure (ICP) was 11 mm Hg and a linear relationship was found between CSF absorption and ICP. The mean Cout was 0.11 ml/min/mm Hg and the lower 95% confidence level was 0.10 ml/min/mm Hg. These values are in accordance with those obtained from previous studies.

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.

Increased brain water content in pseudotumour cerebri measured by magnetic resonance imaging of brain water self diffusion.

Brain water self diffusion was investigated by magnetic resonance scanning in 7 patients fulfilling conventional diagnostic criteria for pseudotumour cerebri. Quantitative diffusion measurements were obtained using single spin echo pulse sequences with pulsed magnetic field gradients of different magnitude. In all patients the diffusion images showed an increased diffusion in various brain regions when compared with the diffusion coefficients for corresponding regions in healthy subjects. In 3 pseudotumour patients the increased self diffusion was localized to the periventricular regions, while 4 patients had increased diffusion in the whole brain. The findings indicate the presence of increased brain water content both intra- and extracellularly suggesting that patients with pseudotumour have two defects of pathogenetical significance: intracellular water accumulation and increased resistance to cerebrospinal fluid (CSF) outflow leading to an interstitial oedema.

A controlled comparison of myelography, computed tomography, and magnetic resonance imaging in clinically suspected lumbar disc herniation.

STUDY DESIGN: A controlled prospective blinded study. OBJECTIVES: To compare the diagnostic power of myelography, computed tomography and magnetic resonance imaging in the diagnosis of low lumbar disc herniation. METHODS: Eighty patients with monoradicular sciatica were examined by myelography, computed tomography, and magnetic resonance imaging, and all underwent subsequent surgery. The images were evaluated twice in a blinded fashion, and the diagnostic power of the modalities was expressed by a decision-analytic regret function. RESULTS: In 57 patients (71%) a disc herniation at the expected level was disclosed at surgery. The largest amount of diagnostic information was gained from computed tomography, followed by magnetic resonance imaging and myelography. Both computed tomography and magnetic resonance imaging were significantly informative, whereas this was not the case for myelography. CONCLUSION: The results indicate that computed tomography or magnetic resonance imaging should be the first choice for imaging in patients with suspected lumbar disc herniation.