Ketoconazole in the treatment of cryptococcosis of the central nervous system.

Two patients with cryptococcosis of the CNS were treated with ketoconazole (KTZ), an imidazole derivative with fungistatic properties: they had either failed standard therapy (Amphotericin-B + 5-Fluorocytosine) or suffered intolerable side-effects to it. Both patients were administered KTZ 800 mg/day as monotherapy for six months without interruption and both responded. One month after KTZ therapy was withdrawn, however, a relapse of the infection was seen in one case. Side-effects were minimal during the trial of treatment. KTZ could be a useful drug in some cases of neurocryptococcosis.     

Wall-eyed bilateral internuclear ophthalmoplegia in central nervous system cryptococcosis.

Only one case of wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) has been described in central nervous system cryptococcosis. The disorder was initially unilateral, then became bilateral with skew deviation and vertical upgaze deficit. We report a case of WEBINO in central nervous system cryptococcosis in a patient with acquired immune deficiency syndrome. Magnetic resonance imaging revealed high signal on T2 images in the right midbrain, left frontal vertex, left splenium, and cerebellum. With treatment, the internuclear ophthalmoplegia improved; however, the convergence insufficiency remained. Disruption of input from cortical supranuclear locations or the region of the rostral interstitial nucleus of the medial longitudinal fasciculus has been proposed as a mechanism in the absence of convergence. This correlates in our patient with the lesions seen on magnetic resonance images.     

Isolated central nervous system aspergillosis in the acquired immunodeficiency syndrome.

Aspergillus infection involving the central nervous system are unusual, but should be included in the differential diagnosis in patients with the acquired immunodeficiency syndrome and neurologic signs and symptoms. Of the few reported AIDS cases with central nervous system aspergillosis, the majority have had focal brain abscesses. We report an atypical case that presented as a basal meningitis with pontine infarction secondary to invasive Aspergillus sinusitis.     

Response of central nervous system aspergillosis to voriconazole

Fungal infections of the central nervous system (CNS) usually present as subacute meningitis. Other manifestations include mass effect and focal neurological deficits. Cerebrospinal fluid (CSF) examination and biopsy of the lesion are helpful in disclosing the organism involved. Aspergillosis presents as brain abscess or granuloma with predominant neutrophils in CSF. Voriconazole is a broad spectrum triazole antifungal agent. It can be given orally and has lesser adverse effects We report a 69-years-old diabetic male, with aspergilloma of para-nasal sinus invading the CNS, who responded well to voriconazole treatment. He discontinued the medication by himself as it was costly. Within a month of stopping the medication, he developed features of subacute meningitis. However he showed clinical improvement after the medication was restarted. The case is reported for the clinical evidence of antifungal activity of voriconazole against aspergillosis.     

Angiitis of the central nervous system.

Angiitis of the central nervous system is a rare disease which may result from numerous causes responsible for the presence of inflammatory lesions of the vascular wall. These inflammatory lesions may sometimes be associated with necrosis. Cerebral vessels of all sizes may be involved. The clinical presentation is highly variable, with focal to diffuse manifestations and acute to chronic evolution. Angiography is the cornerstone diagnostic procedure, showing multiple segmental stenoses of the cerebral arteries sometimes separated by fusiform dilatations. Although suggestive, this angiographical pattern is not unequivocal and other causes must be carefully ruled out. Only cerebral and/or leptomeningeal biopsy can provide a definite diagnosis of cerebral angiitis but this invasive diagnostic procedure is not performed in the majority of cases. Among the numerous causes of cerebral angiitis, one can individualize infectious diseases, primary systemic angiitis with cerebral involvement, angiitis secondary to various systemic diseases and other miscellaneous causes such as drug abuse or neoplasm.     

Histoplasmosis of the central nervous system.

Histoplasma capsulatum infection of the central nervous system is extremely rare in the United Kingdom partly because the organism is not endemic. However, because the organism can remain quiescent in the lungs or the adrenal glands for over 40 years before dissemination, it increasingly needs to be considered in unexplained neurological disease particularly in people who lived in endemic areas as children. In this paper a rapidly progressive fatal myelopathy in an English man brought up in India was shown at necropsy to be due to histoplasmosis. The neurological features of this infection are reviewed.     

Slow infections of the central nervous system.

This review describes the recent advances in slow infections of the nervous system emphasizing the pathogenetic aspects of these diseases. A theoretical model for the pathogenesis of subacute sclerosing panencephalitis (SSPE) is proposed, illustrating the factors that may affect host response to the measles virus and allow it to persist and produce the panencephalitis. The isolation of an oncogenic virus from progressive multifocal leukoencephalopathy (PML) has implications in the consideration of a viral etiology for some brain tumors. The agent responsible for the transmissibility of kuru and Creutzfeldt-Jakob disease (CJD) remains uncharacterized despite recent interest in viroids and abnormalities in replication of cell membranes. The epidemiological data on multiple sclerosis suggests an exposure to an infectious agent at an early age of life modified by the host response. No specific agent has been consistently associated with multiple sclerosis. Amyotrophic lateral sclerosis (ALS), Parkinson's disease, Mollaret's meningitis and Behcet's disease are other examples where a virus is suspect but unproven. The ability of viruses to persist in the host for months to years has linked many chronic neurologic diseases to an infectious agent, enlarging the spectrum of disease caused by viruses.     

Rosai-Dorfman disease of the central nervous system.

Rosai-Dorfman disease (RDD) is an idiopathic, non-neoplastic, lymphoproliferative disorder characterized by sinus histiocytosis and massive lymphadenopathy. When RDD involves the central nervous system the lesion simulates a meningioma. Histological and immunohistochemical confirmation is essential for a definitive diagnosis. In this paper, ten cases of RDD confined to the central nervous system are reported. Another case with orbital RDD was excluded. Nine cases involved the cranial cavity alone; in one, the cervical extradural region was also involved. Treatment consisted of surgical excision or biopsy. Histology and immunohistochemistry revealed a mixed cell population of predominantly mature histiocytes with evidence of emperipolesis and strong positivity for S100 protein in all cases. No recurrence was observed during follow up ranging from three months to eight years.     

Fungal infections of the central nervous system.

This review discusses a practical approach to the patient with possible fungal infection of the central nervous system (CNS). Difficulties in establishing the diagnosis come from the nonspecific clinical syndromes (subacute meningitis, meningoencephalitis, and brain abscess) and the low isolation rate of fungi from cerebrospinal fluid (CSF). Helpful diagnostic clues often come from knowledge of the patient's geographic travels, risk factors, evidence of systemic organ infection, and fungal serologic tests. Standard and new antifungal agents are evaluated and the initial and suppressive drug management of the common fungal infections is presented.     

Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema.

Apolipoprotein E has been implicated in modifying neurological outcome after traumatic brain injury, although the mechanisms by which this occurs remain poorly defined. To investigate the role of endogenous apolipoprotein E following acute brain injury, noninvasive magnetic resonance imaging was performed on anesthetized mice following closed head injury. Effacement of the lateral ventricle was used as a radiographic surrogate for cerebral edema. At 24 hours following injury, apolipoprotein E-deficient animals had a greater degree of cerebral edema as compared to matched controls. In addition, the brains of apolipoprotein E-deficient animals had a significantly greater upregulation of tissue necrosis factor alpha messenger ribonucleic acid as compared to controls as early as 1-hr post injury. Thus, modulation of the endogenous central nervous system inflammatory response may be one mechanism by which apolipoprotein E affects outcome following acute brain injury.     

Neurotoxins and degeneration in the central nervous system.

Numerous examples exist where neurotoxins have been shown to induce selective death of certain groups of nerve cells. While the peripheral nerves are particularly vulnerable, neurotoxins are also capable of generating models of the major degenerative disorders of the central nervous system: dementia of Alzheimer's type, Parkinsonism, and amyotrophic lateral sclerosis. Important organic toxins, in this context, include certain pyridines, amines, aminoacids, nitriles, hexacarbons, and sulphides. Inorganic toxins include free radicals and certain metals. Toxins may also be classified according to their origin--exogenous or endogenous. This review will not consider neurological damage that can result from exposure to alcohol, or neurological adverse reactions to medications.     

Communication and computation in the central nervous system.

Some aspects of the communicational and computational features of the central nervous system (CNS) are presented. We have suggested the existence in the CNS of two types of electrochemical transmission, namely the wiring transmission (WT) and the volume transmission (VT), where WT is the classical type of neural transmission based on the physical substrate of neural chains, whereas VT consists of chemical signals diffusing in the extracellular fluid and reaching receptors on neuronal cells located far away from the signal release site. Experimental data supporting this hypothesis as well as the functional characteristics of both types of transmission are reported.     

Immunolocalization of cathepsin D in the human central nervous system and central nervous system neoplasms

The cellular distribution of the lysosomal proteinase cathepsin D was studied in a series of 76 neoplasms and 18 non-neoplastic tissues from the human central nervous system, using a well-characterized polyclonal antibody in a peroxidase-antiperoxidase technique. In the normal and developing brain, cathepsin D is confined to neurons and choroid plexus epithelium. Strong granular cytoplasmic staining was present in neuronal and choroid plexus neoplasms, and in reactive macrophages. A large variety of other neoplasms also exhibited positive cytoplasmic staining, albeit usually of a weaker diffuse type. Cathepsin D cannot be considered a specific marker for neuronal or choroid plexus neoplasms, but the antiserum used in this study may be of value in antibody panels for the investigation of these tumours. Its localization may also be of value in embryological studies, particularly in the cerebellum, and in investigations of steroid hormone receptor-associated proteins in meningiomas and Schwannomas.