Diagnosis, treatment, and outcome of pituitary tumors and other abnormal intrasellar masses. Retrospective analysis of 353 patients.

We reviewed the clinical features, essential laboratory data, pituitary imaging findings (computerized tomography and magnetic resonance imaging), management, and outcome of 353 consecutive patients with the presumptive diagnosis of pituitary tumor investigated from January 1984 through December 1997 at University Hospital, Lausanne, Switzerland. In 18 cases primary empty sella turcica was diagnosed, and in 13 cases of pseudacromegaly there were no endocrine abnormalities. The remaining 322 patients disclosed abnormal pituitary masses, including 275 pituitary adenomas, 18 craniopharyngiomas, 6 cases of primary pituitary hyperplasia, 6 intrasellar meningiomas, 6 cases of distant metastases, 4 intrasellar cysts, 2 chordomas, 1 primary lymphoma, and 1 astrocytoma. Biologic data and immunohistochemical analysis of the excised tissues demonstrated that prolactinomas and nonsecreting adenomas (NSAs) were the most frequent pituitary tumors (40% and 39%, respectively), followed by somatotropic adenomas with acromegaly (11%) and Cushing disease (6%). In contrast with the vast majority of NSAs, which significantly expressed glycoprotein hormones in tissue without secreting them, there was a small group of glycoprotein hormone-secreting adenomas (2%), which had a more severe clinical course after surgery. Thirty-eight pituitary masses were incidentally discovered, most of them NSAs. The expansion of pituitary adenomas into the right cavernous sinus was twice as frequent as to the left cavernous sinus. For the differential diagnosis of hyperprolactinemia, basal prolactin (PRL) levels above 85 micrograms/L, in the absence of renal failure and PRL-enhancing drugs, and a PRL increment of less than 30% after thyrotropin-releasing hormone (TRH) accurately ruled out functional hyperprolactinemia due to NSA, and were typical of prolactinomas. For screening and follow-up of acromegaly, basal growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, as well as the paradoxical GH response to TRH (present in 2/3 acromegalic patients), could be used as convenient tools, but the most accurate test for diagnosis and prediction of outcome after therapy was GH (lack of) suppression during oral glucose tolerance test. In Cushing disease, single evening plasma cortisol was as good as the overnight dexamethasone suppression test for screening, and a combined dexamethasoneovine corticotropin-releasing hormone (oCRH) test was as accurate as the long dexamethasone suppression test to confirm the diagnosis. Bilateral inferior petrosal sinus catheterization coupled with oCRH test confirmed the pituitary origin of excess adrenocorticotropic hormone (ACTH) in all patients, including those with normal pituitary on magnetic resonance imaging (50% of the cases). However, this procedure failed to predict tumor localization correctly within the pituitary in 21% of patients. Pituitary cysts, meningiomas, and craniopharyngiomas with an intrasellar component were correctly diagnosed based on pituitary imaging in 75%, 67%, and 44% of cases, respectively. The remainder, as well as the cases of pituitary hyperplasia, metastases, and other less frequent pathologies, were initially diagnosed as NSAs or as masses of unknown nature. When surgery was indicated, pituitary adenomas and other intrasellar masses were operated on by the transsphenoidal route, with the exception of 100% of meningiomas, 83% of craniopharyngiomas, and 10% of NSAs, which were operated on by the transcranial route. Favorable late surgical outcome of prolactinomas could be predicted by a restored PRL response to TRH. However, dopamine agonist (DA) therapy, usually resulting in satisfactory control of PRL levels and in tumor shrinkage, progressively displaced surgery as primary treatment for prolactinomas throughout the study period. After full-term pregnancy, the size of prolactinoma decreased in 7 of 9 patients, and PRL was normal in 2. Surgery was the first treatment for NSAs, with a tumor rela

Immunolocalization of neuropeptide Y in human pituitary tumours.

Neuropeptide Y (NPY) gene is expressed in human pituitary gland where its function is partially elucidated. NPY could act as a neuroendocrine modulator within this gland. This study was undertaken to assess whether NPY expression is correlated to various pathological situations. Using a highly specific anti-NPY monoclonal antibody, immunohistochemistry analysis was performed in surgically removed pituitary glands. The study included biopsies from 112 human pituitary adenomas, 12 hyperplastic glands and normal anterior pituitary tissues in 34 cases. NPY is immunodetected in 33% of all adenomas, 25% hyperplastic glands and 12% of non-tumoral pituitary gland. NPY expression was significantly higher in adenomas compared to the normal gland. However, no correlation was observed between NPY content and the type of hormonal secretion, sex, age and the status of tumour proliferating potential.

Differential expression of triiodothyronine receptors in schwannoma and neurofibroma: role of Schwann cell-axon interaction.

Regulation of gene expression in Schwann cells may be determined, at least in part, by the interaction of these cells with axons. Two peripheral nerve tumors, neurofibroma and schwannoma, represent good tools for studying Schwann cell activity in the presence or absence of axon action. In the present work we studied the expression of triiodothyronine receptors (T3R) by Schwann cells in these two tumors and also in adult normal sciatic nerve. Confirming the results of the histological examination, immunostaining of the neurofilaments showed the presence of fascicles or scattered axons in all neurofibroma sections studied. In these neurofibromas, Schwann cells did not express T3R immunoreactivity. Furthermore, in adult normal sciatic nerve, Schwann cells which ensheathed axons were devoid of any T3R expression. In contrast, in schwannoma, the complete absence of axons was demonstrated by the lack of neurofilament immunostaining. Here, Schwann cells deprived of axonal interaction displayed clear T3R immunoreactivity. In schwannoma cell cultures, Schwann cells continued to express T3R, even in cultures treated with medium that had been conditioned with rat sensory neurons. On the basis of these results, we suggest that, beside the possible regulatory mechanisms for T3R, the synthesis of T3R is regulated, at least in part, by Schwann cell-axon interaction.

[Neuritis of multiple cranial nerves in idiopathic focal pachymeningitis]. / Multinévrite crânienne dans le cadre d'une pachyméningite focale idiopathique.

A 76 years old patient suffering from insulin dependent diabetes presents a multiple, bilateral and asymmetric cranial neuropathy involving on the left side the cranial nerves VIII, IX with a participation of the efferent autonomic fibers of the nerves VII and IX (xerostomia) and the nerve XII, and involving on both sides the nerves VII and X. Like it is known from literature the nerve XI was spared, probably because of the more caudal emergence from the brainstem. The disease was preceded by a violent otalgia on the left side which was initially interpretated as a malignant external otitis. This affection was associated with an inflammatory syndrome that was easily monitored by the blood sedimentation rate. The course was favorable but marked by fluctuations of the neurological deficits. The MRI shows a pachymeningitis localised at the beginning in the medial fossa and on the cerebellar tentorium, later on the left parieto-occipital convexity. The diagnosis of a focal idiopathic pachymeningitis was confirmed by excluding different other affections like inflammatory, tumoral and infectious diseases, by using MRI examinations, CSF analysis and especially meningeal biopsy. It is a rare inflammatory disease of unknown origin with potentially persistent neurological deficits. We discuss the differential diagnosis and the therapeutical possibilities, which consist in a long term immunosuppression with corticosteroids and azathioprine.

[Critical analysis of the results of muscle biopsies and of the methods used in 889 cases of neuromuscular disorders]. / Analyse critique des résultats de biopsies musculaires et de la méthodologie utilisée dans 889 cas d'affections neuromusculaires.

The contribution of muscle biopsies to the diagnosis of neuromuscular disorders and the indications of various methods of examination are investigated by analysis of 889 biopsies from patients suffering from myopathic and/or neurogenic disorders. Histo-enzymatic studies performed on frozen material as well as immunohistochemistry and electron microscopy allowed to provide specific diagnoses in all the neurogenic disorders (polyneuropathies and motor neuron diseases), whereas one third of myopathies remained uncertain. Confrontation of neuropathological data with the clinical indications for histological investigations shows that muscle biopsies reveal the diagnosis in 25% of the cases (mainly in congenital and metabolic myopathies) and confirm and/or complete the clinical diagnosis in 50%. In the remaining cases with non specific abnormalities neuropathological investigations may help the clinician by excluding well defined neuromuscular disorders. Analysis of performed studies and results of investigations show the contribution and specificity of each method for the diagnosis. Statistical evaluation of this series indicates that cryostat sectioning for histo- and immunochemical and electron microscopy increases the rate of diagnoses of neuromuscular diseases: full investigation was necessary for the diagnosis in 30% of the cases. The interpretation of the wide range of pathological reactions in muscles requires a close cooperation with the clinician.

Spinal tumour due to primary hyperparathyroidism causing sciatica: case report.

We report a unilateral intraspinal cyst-like lesion adjacent to the lamina and facet joint at the L4-L5 level producing sciatica. Histological examination revealed multinucleate giant cells suggesting a brown tumour. Further studies disclosed primary hyperparathyroidism, whose first manifestation was the lumbar nerve root compression. Previous cases of compression of neural structures by spinal brown tumours are reviewed and a radiological differential diagnosis is presented.

Skull base chordomas: presentation of six cases and review of the literature.

Chordomas are uncommon tumours occuring from remnants of the notochord. They are mainly localized in the sacrococcygium, the spine and the skull base. We focused our study on skull base chordomas and reviewed 531 published cases and 6 cases diagnosed in our institution. The six cases diagnosed at our hospital are described with a special mention of a unique case presenting with meningitis. Clinical features, radiology, histopathology and survival with different treatments are reviewed. Skull base chordomas can occur at any age and are slightly more frequent in males. Patients complain most often of diplopia and headaches. Abducens nerve palsy is the commonest neurological finding. Radiological examination should include both CT-scan which shows extensive osteolysis, calcifications and contrast enhancement and MRI for topographical definition. Metastases rarely occur. Treatment remains controversial but combined surgery and radiotherapy is the best treatment with a 5 year survival rate of 75%.

Giant cell tumor of the orbit.

Giant cell tumors of the skull are very rare and usually occur in the sphenoid bone. The authors report the case of a 10-year-old boy with such a tumor involving exclusively the roof of the left orbit. He presented essentially with edema of the left superior eyelid and diplopia. Computed tomographic examination and magnetic resonance imaging delineated the lesion, which was radically removed via a left fronto-orbital craniotomy. Some aspects of this rare neoplasm are reviewed.

Pilocytic cerebellar astrocytoma in adults: case report.

A case of cerebellar pilocytic astrocytoma is reported. This tumor occurs typically in the first two decades of life and is seldom reported in adults. The 42-year-old patient presented with occipital headaches, nausea, and unsteady gait. Nystagmus and right dysmetria were noted. A CT scan showed a hypodense, nonenhancing, voluminous, right hemispheric cerebellar cyst. Magnetic resonance imaging showed a nodule in the wall of the cyst which became hyperintense with gadolinium. The mass was resected through a small occipital craniotomy. Neuropathological examination revealed a juvenile pilocytic astrocytoma.

Cellular schwannomas of the intracranial and intraspinal compartment: morphological and immunological characteristics compared with classical benign schwannomas.

The concept of cellular schwannoma as an unusual benign tumor is well established for peripheral nerves but has never been tested in neurosurgical series. In order to test the validity of this concept in cranial nerves and spinal roots we performed an analysis of the clinical and morphological characteristics of 12 cellular and 166 classical benign schwannomas. Immunohistochemical detection of antigen expression in Schwann cells including proliferating cell nuclear antigen (PCNA) was also performed. This study shows that cellular schwannomas in neurosurgical series manifest at a lower age than the classical benign variant and occur mainly in the spinal roots. Mitotic activity and sinusoidal vessels appear more frequently in cellular schwannomas and constitute with high cellularity, the most valuable criteria separating both entities. The postoperative course in both types of tumors was free of metastases or sarcomatous changes. Immunoexpression of S-100 protein, vimentin, epithelial membrane antigen and glial fibrillary acidic protein is not statistically different between the two variants. In contrast, PCNA is more highly expressed in cellular schwannomas. These These results confirm the concept that cellular schwannomas are a clinico-pathological variant of benign schwannomas and provide significant support for the introduction of this entity in neurosurgical oncology.

[A clinicopathological case of progressive aphasia]. / Un cas clinico-pathologique d'aphasie progressive.

We report the case of a 59-year old right-handed woman presenting with progressive aphasia without any other neurological deficit and characterized by anomia, agramatism and auditory comprehension difficulties. CT scan showed no abnormalities. Four years later, aphasia was complete but neurological examination was normal. CT scan disclosed a mild cortico-subcortical cerebral atrophy with slight widening of both sylvian fissures. The results obtained with the Wisconsin Card Sorting Test and the Raven's Matrices showed only minor deficits. The IQ (WAIS) was 90. During the following 6 years the patient remained fully self-sufficient and carried out her homework normally. At that time MRI showed progression of cerebral atrophy more pronounced on the left side. Besides a rapid deterioration, twelve months later she developed severe dementia and died 13 years after the onset of the illness. Brain examination disclosed a severe atrophy (brain weight: 880 g) prominent in both frontal lobes and in the anterior perisylvian structures, more pronounced on the left side. There were no vascular lesions. Microscopy revealed widespread neuronal loss and astrocytic fibrillary gliosis confined to cortical areas and vacuolation in the superficial layers. Neurofibrillary tangles and neuritic plaques were found in the most atrophic areas but not in sufficient number to fulfill the histological criteria for Alzheimer's disease. There were no neuropathological changes of Pick's disease or subcortical degeneration. Previous microscopical studies of primary progressive aphasia showed non specific, mostly lobar atrophy similar to that observed in our case, although Alzheimer, Pick and Creutzfeldt-Jakob diseases have been reported. This neuropathological heterogeneity confirms that progressive aphasia is a non-specific language disorder mostly observed in lobar forms of brain degeneration.

Cyst of the ligamentum flavum: report of six cases.

Six cases of cyst of the ligamentum flavum with compression of a lumbar nerve root are reported. All patients exhibited recurrent back pain and sciatica. Investigation included computed tomography, myelography, or both. The correct diagnosis was reached before operation in only half the patients. High-resolution computed tomography performed in the four last patients outlined the cystic lesion with its low-density center. Surgical excision was performed in all patients. Microscopic examination showed a dense fibrous cyst arising from the ligamentum flavum. The lumen contained myxoid or necrotic material, but no epithelial lining. Cysts of the ligamentum flavum must be considered in the differential diagnosis of causes of sciatica. A firm radiological diagnosis may, at present, still require myelography combined with high-resolution computed tomography. Differentiation from synovial or ganglion cysts of the spine is discussed.

Respiratory failure and unilateral caudal brainstem infarction.

We report clinicotopographic correlations in 2 patients with central hypoventilation and unilateral infarct in the caudal brainstem. One patient had nearly complete loss of ventilation involving both automatic and voluntary components. He showed no ventilator response during a CO2 retention test (PaCO2 62 mm Hg, PaO2 82 mm Hg), while consciousness was preserved until death. The infarct involved the reticular formation, nucleus tractus solitarius, nucleus ambiguus, and nucleus retroambiguus on the right but spared the dorsal motor nucleus of the tenth cranial nerve, and sensory and corticospinal tracts. The second patient showed hypoventilation more selectively involving automatic responses (Ondine's curse). The infarct involved the medullary reticular formation and nucleus ambiguus but spared the nucleus tractus solitarius. We suggest that unilateral involvement of pontomedullary reticular formation and nucleus ambiguus is sufficient for generating loss of automatic respiration, while associated lesion of the nucleus tractus solitarius may lead to more severe respiratory failure involving both automatic and voluntary responses.

[Nervous system pathology in AIDS: results of a collaborative autopsy study from Switzerland]. / Pathologie des zentralen Nerven-systems bei Aids: Resultate einer kollaborativen Autopsiestudie aus der Schweiz.

Neuropathological lesions were studied in a consecutive autopsy series of 206 cases, comprising 61% of all patients who died of Aids in Switzerland between April 1981 and December 1988. Central nervous system involvement was found in 84% of the patients, and 17% showed multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, cerebral toxoplasmosis was most frequent (24%), whilst among the viral opportunistic infections, cytomegalovirus (CMV) encephalitis was most frequent (7%). A nodular encephalitis consisting of disseminated microglial nodules without morphological or immunocytochemical evidence of CMV occurred in 13.5% of the patients. The majority of these cases showed evidence of extracerebral CMV infection. Progressive multifocal leukoencephalopathy (PML) was observed in 6% of the patients and was associated with widespread tissue destruction and cyst formation. HIV encephalopathy occurred in 38 patients (18%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 22 patients and was characterized by a diffuse demyelination and gliosis of the white matter with little inflammatory infiltrates and scattered multinucleated giant cells which were immunoreactive to HIV antigens. MGCE was found in 16 patients and was characterized by clusters of macrophages, lymphocytes, and HIV-immunoreactive multi-nucleated giant cells. In our view, PDL and MGCE represent two opposite variants of HIV-induced encephalopathies with numerous intermediate manifestations.

Symptomatic xanthogranuloma of the third ventricle: report of two cases and review of the literature.

Two patients with symptomatic xanthogranuloma of the third ventricle are presented. Both presented with a short history of increased intracranial pressure owing to hydrocephalus secondary to obstruction of the foramina of Monro. Computed tomography scanning demonstrated in both cases a round hypoisodense nonenhancing mass localized in the third ventricle, with dilatation of the lateral ventricles. Macroscopically complete surgical removal by a right transventricular approach was achieved in both patients. Eleven cases of xanthogranulomas of the third ventricle, including our own, have been published in the literature. The pathogenesis, clinical and radiological features, differential diagnosis, and treatment of this rare benign lesion are briefly discussed.

Reversible emetine-induced myopathy with ECG abnormalities: a toxic myopathy.

A young anorexic woman is described with a history of progressive muscle weakness following chronic ingestion of syrup of ipecac that was used in an attempt at weight control. Electrocardiogram (ECG) showed T-wave inversion in all leads and prolongation of the Q-T interval. Electromyography was abnormal. Muscle biopsy revealed a randomized, generalized, predominantly type-2 fibre atrophy and structural alterations in oxidative enzyme stains, such as targetoid and moth-eaten fibres. A few necrotic cells were actively phagocytosed. Electron microscopy revealed severe sarcomeric abnormalities with Z-line streaming, myofibrillar disorganization and increased lysosomal activity. After discontinuation of ipecac syrup, the patient noted a gradual improvement in her condition. The ECG became normal. Emetine and related drug-induced myopathies are uncommon but are of experimental interest because of their effects on mitochondria and the light they shed on autophagic mechanisms in muscle.

Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland.

Neuropathological changes were studied in a consecutive autopsy series of 135 cases, comprising 73% of all patients who died of AIDS in Switzerland between April 1981 and December 1987. Central nervous system involvement was found in 119 patients (88%), 19 of which had multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, encephalitis due to Toxoplasma gondii was most frequent and occurred in 35 patients (26%), followed by central nervous system infection with Cryptococcus neoformans, which was found in five patients (4%). Cytomegalovirus (CMV) encephalitis was present in 14 patients (10%). Disseminated microglial nodules without morphological or immunocytochemical evidence of CMV was encountered in 18 patients (13%). However, in all but two of these patients there was evidence of extracerebral CMV infection, suggesting that CMV was responsible for these nodular encephalitides. Nine patients (7%) had progressive multifocal leukoencephalopathy (PML); in five of these, demyelination was associated with extensive tissue destruction and cyst formation. HIV-associated encephalopathy was observed in 21 patients (16%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 13 cases and characterized by diffuse pallor and gliosis of the cerebral and cerebellar white matter with scattered multinucleated giant cells, but without significant inflammatory response. MGCE was found in eight patients and characterized by clusters of numerous multinucleated giant cells, rod cells, macrophages, lymphocytic infiltrates and occasional necroses. In our view, PDL and MGCE represent the two opposite variants of HIV-induced encephalopathies, with overlapping intermediate manifestations.