Postoperative treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists decreases tumour remnant growth.

OBJECTIVE: There is no consensus as to the optimal postoperative treatment of patients with clinically nonfunctioning pituitary adenomas (NFPA) in whom total tumour removal has not been achieved. In this study we assessed whether dopamine agonist (DA) treatment can prevent postoperative remnant enlargement in NFPA. DESIGN AND METHODS: Thirty-three patients (25 men/8 women; mean age, 61.7 +/- 11.2 years; mean follow-up, 40.6 +/- 4.8 months) were treated with DA, and their outcome was compared to that of 47 untreated patients (33 men/14 women; mean age, 59 +/- 2 years; mean follow-up, 42.9 +/- 4.2 months). RESULTS: Tumour mass decreased or remained stable in 18/20 patients in whom DA treatment was initiated upon detection of residual tumour on postoperative MRI (group I). In 13 subjects (group II), DA therapy was started when tumour remnant growth became evident during the course of routine follow-up. Tumour growth stabilized or decreased in 8/13 (61.5%) of these patients. In contrast, tumour size remained stable in only 38.3% (18/47) of the untreated subjects (P < 0.0001 for comparisons among the three groups) and increased in the remaining 29 patients. Tumour enlargement free mean survival time was 103.7 +/- 8.8 months (CI 86.3-121) for group I, 43.9 +/- 9.6 months (CI 25.2-62.8) for group II and 36.7 +/- 3.8 (CI 29.2-44.2) for the control group (P = 0.0017). Treatment vs. control hazard ratio for tumour enlargement was 0.135 for group I (P = 0.007, 95% CI 0.032-0.577) and 0.892 for group II (P = 0.817; 95% CI 0.34-2.34). CONCLUSIONS: Dopamine agonist therapy is associated with a decreased prevalence of residual tumour enlargement in patients with nonfunctioning pituitary adenomas, particularly when treatment is instituted before tumour remnant growth is detected.

Clinical characteristics of elderly patients with a cautious gait of unknown origin.

OBJECTIVE: To evaluate and systematically characterize a group of older adults with disturbed gait of unknown origin. DESIGN: Cross-sectional study. SETTING: Outpatient clinic in a movement disorders unit. PARTICIPANTS: Twenty-five patients (mean age 78.4 years) with a disturbed gait of unknown origin were compared with twenty-eight age matched "healthy" controls (mean age 78.2). MEASUREMENT: Detailed medical history, geriatric and neurological assessments. RESULTS: Patients walked more slowly (P<0.0001) and with shorter strides (P<0.0001) compared with controls. Muscle strength was lower, and static and dynamic balance and gait performance were worse among the patients (P<0.0001). The patients also tended to be more depressed (P<0.0001),more anxious (P<0.002), had a greater fear of falling (P<0.0001) and had lower scores on the Mini-Mental State Examination (P<0.005). There was no difference in the frequency of cerebellar or pyramidal signs in the two groups. However, neurological testing revealed that extrapyramidal (P<0.0001) and frontal release signs (P<0.0001) were more common among the patients. Neuroradiological findings were rare among the patients and they did not explain the changes in gait speed or fear of falling. CONCLUSIONS: Older adults with a disturbed gait of unknown origin appear to share common characteristics. They walk more slowly than "healthy" controls with increased unsteadiness and with excessive fear of falling. The extrapyramidal, frontal lobe, and limbic systems apparently play an important role, to different degrees, in what can be viewed as a multisystem neurodegenerative syndrome clearly different from "aging."

Early CT changes and outcome of ischemic stroke.

Although recombinant tissue plasminogen activator (rt-PA) was rapidly implemented as part of the emergency care of acute stroke, its use in daily clinical practice still remains controversial in many countries. The most important question is criteria for careful selection of subgroup of patients for this treatment. It has been hypothesized that early computed tomography (CT) changes of ischemia are risk factors for symptomatic intracerebral hemorrhage and poor outcome. We conducted a prospective outcome study of patients with acute ischemic stroke (IS) admitted to the hospital within 6 h of symptom onset. Experienced neuroradiologists blind to the clinical outcome of the patients read all CT scans carried out in the emergency room. Early CT changes were defined as in European Cooperative Acute Stroke Study (ECASS) 2. There were 150 patients (75 males, mean age 72.5 +/- 9.0) with acute IS (54.7% with mild stroke and 45.3% with severe stroke). Early CT changes were presented with tissue hypodensity - 55.7%, effacement of sulci - 41.3%, hyperdensity of middle cerebral artery (MCA) - 13.3%, hypodensity of lentiform - 20.7%, loss of insular ribbon sign - 28.7%. Follow-up after 30 days showed that 44% of the patients were discharged home, 20% were discharged to rehabilitation facilities, 22% were discharged to chronic care institutions and 14% died. Data were statistically analyzed. Our data suggest that early signs on CT scan could not predict outcome of patients with acute IS.

Postoperative surveillance of clinically nonfunctioning pituitary macroadenomas: markers of tumour quiescence and regrowth.

BACKGROUND: Postoperative management of clinically nonfunctioning pituitary adenomas (NFPA) presents difficult challenges. There are no good serum markers for presence or growth of the tumour, medical treatment is not effective and radiotherapy carries the risk of significant side-effects. OBJECTIVE: The purpose of this study was to investigate the natural history and biological behaviour of surgically treated NFPA, with a special effort to identify characteristics indicative of a more aggressive course that could assist in the clinical decision-making process. STUDY DESIGN: Patients operated on at our institution for NFPA undergo uniform routine clinical follow-up at the endocrine clinic. Magnetic resonance imaging (MRI) studies are performed 3, 6 and 12 months after transsphenoidal surgery and yearly thereafter for the first 5 years. Subsequently, imaging is performed once every 2 years or as clinically indicated. From 1992 onwards, no patient received immediate postoperative radiation therapy. PATIENTS: One hundred and twenty-two patients (78M/45F) operated on at our institution since 1989 and with a minimal follow-up of 1 year comprised the study group. MEASUREMENTS: Tumour size and characteristics were determined by MRI using a modification of Hardy's and Wilson's classifications. Maximal tumour height was also recorded and the information was routinely stored in a computerized database. RESULTS: Mean (+/- SD) follow-up was 51 +/- 31 months. Fourteen patients received postoperative radiation therapy. Subsequent tumour growth was observed in five of them, reduction in tumour size in four and no size changes in five. One hundred and eight patients did not receive postoperative radiation. Tumour enlargement occurred in 41 of 78 and in six of 30 patients with and without residual tumour after operation (P = 0.0024). The presence of cavernous sinus invasion before surgery [P = 0.02, odds ratio (OR) 2.72; confidence interval (CI) 1.1-6.43] and the extent of suprasellar extension in the postoperative tumour remnant (P = 0.0054 for presence of stage A, OR 4.4; 95% CI 1.5-12.5; and P = 0.012 for presence of stages B or C, OR 16.2; CI 1.8-144) were strong independent predictors of tumour enlargement. CONCLUSION: Our data may ease the selection of patients in whom radiation therapy is likely to be necessary for tumour control, and confirms that close postoperative follow-up is an adequate primary approach in low-risk patients.

High b value q-space-analyzed diffusion MRI in vascular dementia: a preliminary study.

High b value diffusion weighted magnetic resonance imaging (high-b DWI) was used to characterize white matter changes in the brain of patients with vascular dementia (VaD). Hyperintense white matter areas detected by T2-weighted magnetic resonance imaging (MRI) represent lesions, also termed leukoaraiosis that are very common in VaD as well as in other types of dementia. Therefore, the role of white matter changes in the cognitive and memory decline that occurs in VaD patients is still under debate. High-b DWI, analyzed using the q-space approach, is a more sensitive MRI method for detection of white matter changes. High-b DWI revealed massive white matter loss in VaD patients that surpassed the boundaries of T2 hyperintensities. This technique, therefore, might serve as a better indication for the extensive nerve fiber loss in the white matter that is caused by vascular disease.

Morphometric study of the midsagittal MR imaging plane in cases of hydrocephalus and atrophy and in normal brains.

BACKGROUND AND PURPOSE: Midsagittal morphologic changes often aid in the diagnosis of hydrocephalus. Stretching and upward displacement of the corpus callosum, widening of third ventricular recesses, and decreased mammillopontine distance have been described as indicating the possibility of hydrocephalus. Quantitative studies are scarce. We performed retrospective, quantitative analysis to verify and quantify changes in midline morphology that might differentiate hydrocephalus and ventriculomegaly due to atrophy. METHODS: Sagittal MR imaging studies of 22 patients with hydrocephalus and 32 patients with atrophy were analyzed, as were 42 studies with normal findings. The studied parameters included mammillopontine and mammillocommissural distances, callosal height at two points, and the distances between the lines passing through the chiasm (chiasmal line) and the edge of the callosal splenium. Various angles between the chiasmal line and surrounding structures were measured. Similar measurements were done with the line passing through the third ventricular floor segment anterior to the mammillary bodies (third ventricular line). RESULTS: In hydrocephalus, mammillopontine distance decreased, mammillocommissural distance increased, the third ventricular floor segment was concave in most cases, and the chiasmal line rotated clockwise. These changes were not seen in atrophy. Callosal height was increased in hydrocephalus significantly more than in atrophy. CONCLUSION: Specific changes of the midsagittal plane in hydrocephalus, some of which have not been described previously, can be observed and quantified, which might aid in differentiating this condition from atrophy.

Ophthalmic artery calcification in a patient with renal failure.

We report calcification in cranial arteries, including the ophthalmic arteries, visible on CT in a patient with diabetes mellitus and renal failure.

[Presurgical neuropsychological assessment in epilepsy: the Wada test].

37 candidates for epilepsy surgery underwent the intracarotid amytal procedure (IAP; also known as the Wada test) to determine hemispheric speech dominance and memory capacity. 31 demonstrated left hemisphere speech dominance, 2 showed evidence for bilateral language and 4 demonstrated right hemispheric language dominance. Our study supports a correlational relationship between handedness, lesion laterality and age of onset of seizures, as reported in earlier studies. Left-handed patients with a left hemisphere lesion whose seizures began to an early age had a strong tendency for reversed language dominance. Asymmetry of at least 20% in performing the memory test was taken as the cutoff score for demonstrating laterality of lesions. The asymmetry score correctly predicted laterality of lesions in all 28 patients; 6 did not have asymmetry scores and 3 were examined for language only. None of the patients who successfully passed the Wada memory test had any significant postsurgical memory deficits; 1 had transient reduction in verbal memory and 4 who did not pass the test were not operated on for this reason. Our results demonstrate the importance of the Wada test in determining cerebral speech dominance, in predicting post-surgical amnesia, and support its usefulness in predicting laterality of seizure focus in candidates for temporal lobectomy.

Clock drawing test: correlation with linear measurements of CT studies in demented patients.

OBJECTIVES: To investigate a presumed correlation between clock drawing ratings and linear measurements of computerized tomography (CT) studies in demented patients. DESIGN: Blinded evaluations of clock drawing tests and CT studies of elderly dementia patients were conducted by a geriatric psychiatrist and a neuroradiologist. SUBJECTS: Fifty-one community-dwelling elderly subjects meeting the criteria for DSM-IV diagnosis of dementia (Alzheimer's type dementia: N=31; vascular dementia: N=15; "mixed" type dementia: N=5). MATERIALS: Mini-Mental State Examination (MMSE), Cambridge Cognitive Examination (CAMCOG), Clinical Dementia Rating (CDR). CAMCOG derived scored clock drawings were evaluated using adaptations of Shulman et al.'s and Freedman et al.'s methods. CT studies were evaluated using six different linear measurements of brain atrophy described in the literature. RESULTS: Of the CT linear measurements, only the Cerebro-Ventricular Index-2 (CVI-2; bicaudate index) significantly correlated with clock drawing ratings (CAMCOG's clock r=-0.407, p=0.003; Shulman's method r=0.357, p=0.01, Freedman's method r=-0.413, p=0.003) in the dementia group. There was no significant correlation between CVI-2 with demographic (age), cognitive (MMSE, CAMCOG) and clinical (duration of illness, CDR) ratings. Alzheimer's patients generally maintained a significant correlation between CVI-2 and clock drawings, but vascular dementia patients did not; CVI-2 also correlated significantly with the Praxis subtest of the CAMCOG in dementia and Alzheimer's patients but not in the vascular dementia group. Similarly, multiple stepwise regression analysis showed that only CVI-2 but not the other radiological measures studied, was selected as the significant variable to correlated with clock drawing test ratings in the dementia group and Alzheimer's patients. Partial correlation analysis controlling for demographic and clinical variables shows that controlled variables had no significant effect on the relationship between clock drawing ratings and CVI-2. CONCLUSION: A single and easy to perform measure of caudate atrophy correlates specifically and consistently with impairments revealed in the clock drawing test and with a Praxis subtest, suggesting possible caudate involvement with clock drawings in dementia in general and of the Alzheimer's type in particular.

"The disappearing lens": failure of CT to image the lens in traumatic intumescent cataract.

The CT scans of three patients whose eyes were lacerated by trauma failed to demonstrate the lens. A slit-lamp examination of those eyes clearly indicated that the lenses were present behind the iris but that they were swollen and opaque (intumescent cataract). Apparently, a shift of water into the injured lens had reduced the expected hyperdense CT image of the lens to a level that it was no longer discernible.

The use of beta-subunits of gonadotrophin hormones in the follow-up of clinically non-functioning pituitary tumours.

OBJECTIVE: Clinically nonfunctioning pituitary adenomas (NFA) are mostly of gonadotroph origin. However, increased levels of circulating hormones or subunits in patients with NFA usually do not cause clinical symptoms, nor are they used as biological tumour markers. In this study we assessed the value of measuring beta subunits of gonadotrophin hormones in the post-operative follow-up of patients bearing these tumours. DESIGN: Patients harbouring NFA were studied before and three months after transphenoidal pituitary surgery. beta-LH and beta-FSH levels were measured before and following TRH administration on the two occasions. Hormone levels were analyzed in relation to imaging studies performed before and after surgery. PATIENTS: Twenty four patients operated at the Tel Aviv-Sourasky Medical Centre for NFA. RESULTS: Pathological beta-FSH and beta-LH levels were detected in 79% and 60% of patients respectively. beta-LH levels decreased after surgery but there were no significant changes in beta-FSH levels. There was a tendency for tumours with high basal beta-LH levels to be larger and to have a poor surgical outcome. Normalization of beta-LH levels post-operatively was usually associated with a decrease in tumour mass or complete removal of the tumour. Persistent pathological responses of beta-LH to TRH after surgery were common in patients with residual tumours on imaging. Nevertheless there were exceptions to this pattern, rendering post-operative beta-LH levels insufficiently reliable as a marker for the presence of residual tumour. CONCLUSION: Although there appears to be a relationship between beta-LH levels, tumour size and surgical outcome, this association is presently insufficient to allow the routine use of either basal or TRH induced beta-LH responses in the post-surgical follow-up of clinically nonfunctioning pituitary adenomas.

Neuroimaging of children with partial seizures.

The predictive value of abnormal neurological findings on neuroimaging (NI) of children with partial seizures (PS) was studied. The sample comprised 143 children and adolescents with PS from 1979 to 1996. Fifty patients had the following abnormal NI findings: diffuse atrophy and porencephalic cyst (5.6% each), hemiatrophy, tumors, neurocutaneous syndrome brain lesions, and dysgenesis (4.2% each), and arachnoid cyst and hydrocephalus (2.1% each). There were significantly more NI abnormalities among those with simple PS than among the other groups of complex PS or PS with secondary generalization. All cases of porencephalic cyst (n = 8), and hemiatrophy (n = 6) were in the hemiparetic group, all cases of tumor (n = 6) were in the normal group, while most cases of diffuse atrophy were in the mentally retarded group. Patients with abnormal NIs had a significantly earlier age of seizure onset than the others. The chance of finding a treatable abnormality in neuroimaging was 5% for tumors and 2% for arachnoid cysts in the group of patients with PS and normal neurological findings. Neither an abnormality detected in a neurological examination nor the type of seizure are predictive parameters for suggesting the presence of a resectable brain tumor. All patients with newly diagnosed PS should undergo an MRI.

Primary intramedullary spinal melanoma: diagnostic and treatment problems.

A 76-year old female patient with 9 year history of right mastectomy for an infiltrating ductal breast cancer and no evidence of recurrent nor metastatic disease, was admitted due to pain in the lower thoracic area radiating bilaterally to the posterior aspect of the chest wall at the same level, difficulties in micturition, urinary hesitancy, and progressive weakness of the lower limbs. Primary intramedullary spinal tumor was demonstrated by a MRI study of the spine, partially resected, and found to be a malignant melanoma on pathological study. Postoperative irradiation and administration of dexamethasone did not improve the neurologic status.

CT findings in persistent vegetative state following blunt traumatic brain injury.

The use of linear measurements in the analysis of CT scans of TBI patients was found to contribute to the understanding of brain damage and were correlated with outcome in severe traumatic close brain injured patients. The purpose of the present study was to analyse the data obtained by the linear measurements on CT studies of TBI patients who remained in persistent vegetative state following blunt head trauma. All 27 patients included in the study were reported to be neurologically normal prior to injury. Thirteen patients, 11 remaining in persistent vegetative state (responsive but unaware) and two who died, constituted the worst outcome group. Fourteen patients who regained consciousness, underwent multidisciplinary evaluation when their recovery reached a plateau and were ranked according to severity of residual symptoms and outcome. The degree of correlation with the overall vocational outcome parameter with the various radiological indices was calculated as the Spearman rank correlation coefficient, with correction for tied scores. Fisher's z transformation was used to combine results with those of our previous analysis. Three radiological parameters showed a statistically significant correlation with clinical outcome. These were the right and left septum-caudate distance and the cerebroventricular index 2; these showed Spearman rank coefficients of 0.52, 0.45 and 0.48; with two-tailed p-values under 0.01, 0.02 and 0.01 respectively. The width of the third ventricle suggested correlation with the clinical scoring. The findings of the present study point to the importance of loss of deep gray matter of the caudate nuclei and widening of the adjacent part of the lateral ventricles in catastrophic brain injury. This finding may highlight the role of localized ischemic changes, in addition to diffuse axonal injury. Values of over 8 mm for the width of the third ventricle and over 11 mm for septum caudate distance are suggestive of catastrophic and poor prognosis for recovery.

Do silent brain infarctions predict the development of dementia after first ischemic stroke?

BACKGROUND AND PURPOSE: Silent brain infarctions (SBI) are common findings in advanced age, but their relationship to dementia is still uncertain. The present study was designed to evaluate whether SBI predict the development of dementia after first clinical ischemic stroke. METHODS: We blindly studied admission CT scans of 175 consecutive nondemented patients presenting with ischemic stroke that clinically was their first stroke episode. SBI were defined as CT evidence of infarcts not compatible with the acute event. The patients were subsequently followed for their mental state for 5 years. Survival analysis, wherein onset of dementia was the end point, was performed on the total sample population and conducted separately on those with and without SBI at admission. RESULTS: Dementia developed in 56 patients (32%), including 22 of the 63 (35%) with SBI and 34 of the 112 (30%) without SBI. Thus, dementia was not related to SBI. CONCLUSIONS: Our data indicate that SBI do not predict the development of dementia after stroke.

Computed tomography features of cerebral spread of malignant melanoma.

The CT features of cerebral involvement by metastatic malignant melanoma are described in 28 patients. The most common locations of the primary lesion were the trunk and lower limbs. There was a high incidence of extracerebral metastasis at the time of diagnosis of cerebral involvement. Headache and behavioral changes were the most frequent presenting symptoms; 7% of patients with asymptomatic. The cerebral metastases were classified by size (< 1 cm, 1-4 cm, > 4 cm), with more than half measuring 1-4 cm. The larger lesions usually occurred singly. Peritumoral edema was detected in 89% of patients, hemorrhage in 19%, pressure signs on the ventricles in 37%, midline deviation in 15%, and leptomeningeal spread in 11%. No correlation was noted between size of tumor and other radiological features. Unilateral involvement was documented in 44% of cases. In the majority of patients the metastases were located at the periphery of the brain, mostly in the temporal and parietal lobes. Neuroimaging studies of the brain in asymptomatic patients with malignant melanoma may reveal occult metastases and influence the choice of treatment.

CT appearance of a traumatic cataract.

We describe a case of a traumatic cataract that presented on CT as a hypodense lens with a hyderdense rim. The finding reflects the pathogenesis of this entity: a capsular tear and consequent entry of fluid into the lens.