Diagnosis and treatment of carcinoid meningitis: a challenge to the neurologist and oncologist

BACKGROUND: Two clinical types of leptomeningeal metastases from solid tumors are observed: local and disseminated. The former (meningeal carcinomatosis) consists in nodular infiltration of leptomeninges, while the latter (carcinomatous meningitis)--in tumor cells free floating in the cerebrospinal fluid and adhering as a monolayer to the surface of neural structures. Despite the same etiology, the two types of metastasis differ in their clinical manifestation and prognosis. Meningeal carcinomatosis is more frequently diagnosed nowadays due to advances in neuroimaging techniques and the long survival of breast cancer patients. Patients with local, nodular infiltration of leptomeninges may survive many years without symptoms of the disease. On the other hand, carcinomatous meningitis, with its usually violent course and short survival, has become a major problem for oncologists and neurologists because of limited efficacy and considerable toxicity of the treatment. AIMS: The purpose of this article is to review the current knowledge about carcinomatous meningitis in breast cancer patients, taking into account pathophysiology, clinical symptoms, diagnosis, treatment and prognosis. The second aim was to present the authors' experience with the treatment of breast cancer patients suffering from carcinomatous meningitis. MATERIAL AND METHODS: 37 patients with breast cancer and carcinomatous meningitis were treated in the Oncology Center, Warsaw, in the years 2000-2002. Their mean age was 51. The diagnosis was based on results of neurological examination, MRI scan, and the presence of neoplastic cells in the cerebrospinal fluid. In a majority of cases combined treatment was applied, including intrathecal administration of cytostatics, intravenous systemic chemotherapy and radiotherapy. RESULTS: The observation period ranged from 2 to 33 months. A response to the treatment was achieved in 76% of the patients. Their median overall survival was 19 weeks, mean 18 weeks. Seven patients (19%) survived for over 6 months. CONCLUSIONS: The ever-growing incidence of carcinomatous meningitis in the course of breast cancer has become a serious clinical problem for neurologists and oncologists. Treatment results are disappointing, although the combined modality treatment appears to be the best option. New pharmacological approaches to the treatment of meningeal malignancy are required to improve the outcome of patients with carcinomatous meningitis.     

Post-traumatic unilateral atlanto-axial rotatory subluxation in an adult

This retrospective single-patient case report deals with a rare form of spinal trauma, i.e. atlantoaxial rotatory subluxation. The authors present a review of the literature including a classification of rotatory atlantoaxial subluxation types proposed by Fielding, and describe their own experience with treatment of this condition. A case is reported of a 29-year-old woman with a history of head contusion in a car accident. Immediately after the trauma she had the following symptoms: torticollis and neck pain with decreased cervical motion. Atlantoaxial rotatory subluxation of the right C1-C2 articulation was diagnosed by plain radiographs and CT. The patient was treated surgically by an open reduction, unilateral screw fixation of the right CI-C2 articulation (according to Magerl) and posterior C1-C2 wiring with graft. The normal atlantoaxial relation was restored with disappearance of torticollis. At follow-up certain limitation of neck movements due to C1-C2 stabilization persisted. No complications were noted. The patient remains neurologically intact and has radiographic documentation of fusion.     

Advances in the research on immunopathogenesis of myasthenia gravis

Microscopic structure and immunologic function of the thymus gland are outlined, with an emphasis on its role in the process of T and B lymphocytes maturation. Other types of thymic cells are also described, including epithelial and myoid cells that presumably have a central role in initiation of an autoimmunologic process leading to myasthenic symptoms development. A detailed account is presented of issues concerning pathophysiology of myasthenia, the structure of nicotinic acetylcholine receptor (AchR) at neuromuscular junctions, and mechanisms underlying its destruction by autoantibodies. The role of T and B lymphocytes, of various cytokine types, of autoantibodies to various striated muscle antigens, as well as a possible role of genetic and bacterial factors in the development of myasthenia gravis are discussed. In conclusion it is stressed that since recent research findings go beyond the classic theory of myasthenia, a new consistent theory of the disease immunopathogenesis must be created in the future to place all the newly discovered phenomena in a logical conceptual structure.     

Transsphenoidal surgery of intrasellar and perichiasmatic tumors--personal experience

Microsurgical transsphenoidal approach has been for decades an established standard surgical treatment of pituitary adenomas. Actually it offers a safe and rapid midline access to the sellar region with a minimal risk of injury to vascular vessels, the optic chiasm or nerves and the brain. Major limitations of this approach are due to the narrow and deep operating field, with the related possible complications of the pituitary insufficiency and the cerebrospinal fluid rhinorrhea. In this paper the authors present their own experience with transsphenoidal surgery they performed in over 1500 cases during the past 28 years. The history and evolution of the microsurgery are described, including the operative technique, indications and counter-indications, as well as relative advantages and disadvantages of the transsphenoidal approach. Moreover, current modifications of the neurosurgical technique (extended transsphenoidal approaches) and their application in the treatment of non-glandular perichiasmatic tumors are outlined and discussed.     

Intrathecal baclofen in severe spasticity due to multiple sclerosis

Intrathecal administration of baclofen via programmable pump is a highly effective treatment method in severe spasticity resistant to oral medications. The authors describe a case of severe spasticity with tetraplegia and painful (> 10 a day) muscle spasms in the upper and lower limbs and paraspinal muscles, in a patient with clinically definite diagnosis of multiple sclerosis (MS). The 34-year-old female patient with a 15-year history of MS, suffering from lower limb spasticity with pes equinovarus since 1995, was treated with very good results with botulinum toxin injections of calf muscles (14 sessions of Dysport 1500iu till 2002). In the early 2002 she developed tetraplegia with severe, generalized and intractable spasticity. After 4 months of ineffective polytherapy (with high doses of oral baclofen, tizanidine, gabapentine, clonidine, diazepam) and the patient's enormous sufferings (she could neither sit up nor voluntarily change her position in bed), a programmable baclofen pump (Medtronic) was implanted. As soon as a few days after the surgery she could stand, sit and move voluntarily, her painful spasms disappeared, and her bladder catheter was removed. At a 6-month follow-up the effect was stable--she was able to walk a long distance outdoors with the aid of a crutch. The daily dose of the drug is 500 micrograms. No side effects of complications were noted.     

Own experience in surgical treatment of the pineal region and midbrain tumors via the infratentorial approach

Nine cases of tumours located in the pineal and midbrain region in adults operated on between November 1998 and July 2002 in Dept. of Neurosurgery, Central Military Hospital in Warsaw are reported. The patients (2 men and 7 women) were aged from 27 and 69 years (mean age 43.6 years). Their main initial symptoms were caused by hydrocephalus. The histopathological examination revealed anaplastic pinealoma in 2 cases, and pineocytoma, pineal cyst, mesencephalic glial cyst, protoplasmatic astrocytoma, epidermoid cyst, unclear glial scar, and papillary ependymoma in single cases. Five patients had been treated, usually elsewhere, with shunt implantation prior to the surgery. Occipito-suboccipital osteoplastic craniotomy was performed in each case and tumours were totally removed microsurgically via the infratentorial epicerebellar approach. In one case a part of the glial periaqueductal tumour was resected additionally via the fourth ventricle and aqueduct in one stage. Postoperative haematomas in the third and fourth ventricle were found in 2 cases. Main complaints after the surgery included transient diplopia. All the patients improved significantly and resumed their previous life activities. Follow-up ranged from 3 to 44 months. Three patients with pineal tumours and one with a small postoperative ependymoma recurrence were irradiated after the surgery. One patient had been irradiated prior to surgery. Very good results of the surgical treatment of tumours in this area suggest that such patients should be referred earlier to one stage surgical management, as the procedure is easier to perform and shunt implantation may be avoided.     

The frequency of diagnosis of catatonic schizophrenia in hospitals in Lubliniec (1894-1932, 1934-1936, 1970-1999) and Boleslawiec (1958-1999)

AIM: The analysis of the data from the psychiatric hospitals in Lubliniec (1894-1932, 1934-1936, 1970-1999) and Boles?awiec (1958-1999) proved a decrease in frequency of diagnosis of catatonic schizophrenia, what could testify to a decrease in morbidity with this form of schizophrenia. METHOD AND RESULTS: Basing on the facts from scientific literature there was ascertained that the decrease in frequency of diagnosis of catatonic schizophrenia is connected with following causes: firstly, with the changes in nozology, secondly, with the introduction of a new form of therapy and finally, with the fact that here psychological and sociological factors exist which eliminate catatonia as the most expressive form of schizophrenia.     

Associative processes disorders in schizophrenia

This paper tries to approach and systematize knowledge about the character of associative process disorders in schizophrenia. In considering schizophrenia as an illness composed of various symptoms which may lead to different clinical progress, the paper is mainly focused on disorganization of thinking and, consequently, speaking and communication disorders. Authors reviewed various concept of pathogenesis and course of associative process disorders in schizophrenic patients. Special attention was paid to a connectionist model of disturbed associations. This model originates from cognitive psychology and assumes that concepts are represented as networks in the mental lexicon. Following from this model, a hypothesis was presented, claiming that disturbed associations in schizophrenia may be related to abnormalities in semantic networks. Results of research, supporting this hypothesis, were referred. Moreover, authors tried to describe the relationship between associative processes disorders in schizophrenia and abnormalities in neurophysiological (event--related potentials) and neuropathological (MRI) examinations. At least hypotheses describing the role of neurotransmission disorders was presented.     

Where do people with mental disorders are looking for help?

This article presents and discusses the concept of "pathway to psychiatric care". According to literature review, only few people, who meet criteria for mental disorders, reach psychiatrists. Therefore it is important to identify institutions where people with mental disorders look for help. On the basis of World Health Organization programme "Pathway study" authors present institutions in different countries all over the world, which are involved in helping people with mental disorders. In all European centers taken part in the "Pathway study" most of the people who reached psychiatrists had been consulted in primary healthcare first. Project "Pathway study" has been the first research programme related with this topic. It has initiated similar studies in different centers all over the world. Results of those studies show, where outside psychiatric institutions, it is possible to diagnose and treat mentally ill people.     

Retrospective assessment of the antidepressants tolerance in the group of patients with diagnosis of depression and different CYP2D6 genotype

The majority of antidepressants undergo the oxidative biotransformation catalysed by cytochrome P-450, particularly by izoenzyme CYP2D6, whose activity is genetically determined. In many cases poor tolerance of antidepressants depends on CYP2D6 activity. The aim of the study was the evaluation of the relationship between the CYP2Dg genotype and the occurrence of side effects during antidepressive pharmacotherapy.