2007, Vol 7, No 2
Molecular background of tuberous sclerosis complex – part I
Aktualn Neurol 2007, 7 (2), p. 78-84
ABSTRACT

Tuberous sclerosis complex (TSC) is a progressive, dominantly inherited disorder affecting multiple organs mainly: skin, central nervous system, kidneys, lungs, heart and eyes. The prevalance of tuberous sclerosis among general population is estimated to be one in 10,000-30,000. The diagnostic criteria for TS are based on the premise that there are probably no truly one pathognomonic clinical sign but two or more major features are required for formal diagnosis. This disease is associated with mutation in two tumour suppressor genes: TSC1 and TSC2. The main function of protein encoded by TSC1 and TSC2 genes is suppressing signal in the mammalian target of rapamycin (mTOR) pathway. TSC1 is located on chromosome 9q34, the gene contains 23 exons and encodes hamartin. TSC2 is located on chromosome 16p13, the gene contains 41 exons and encodes tuberin. The proteins interact directly with one another and pathological mutations affecting either gene result in TS phenotype. TSC2 protein is the only known GTPase activating protein (GAP) for RAS homolog enriched in brain (RHEB), so that in the absence of functional TSC1/TSC2 complex, RHEB-GTP levels rise. RHEB-GTP levels have a major role in regulating the state of activation of the mTOR complex. Activated mTOR complex has two primary downstream targets: the ribosomal S6 kinases (S6K1 and S6K2) and the eukaryotic initiation factor E4 – binding protein 1 (E4-BP1). The rapamycin is the one of known inhibitors of mTOR and potential drug for TSC.

Keywords: tuberous sclerosis, epidemiology, diagnostic criteria, genes TSC1/2, mTOR, rapamycin
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SYMPOSIUM: VIRUS DISEASES. Arboviruses
Aktualn Neurol 2007, 7 (2), p. 85-95
ABSTRACT

In this review we covered encephalitides and other sequelae of arbovirus infections. A family Flaviviridae along with families Togaviridae, Bunyaviridae, Reoviridae and Arenaviridae had been previously classified as Arboviridae (arthropod-borne). In spite of a significant diversity of viruses of the Arboviridae group, the term “arboviruses” is still useful and widely used. Here we covered viruses spread by ticks: tick-borne encephalitis virus, Powassan, Russian spring summer encephalitis virus, Kyasanur forest disease virus, Omsk hemorrhagic fever virus, louping ill and by mosquitos: yellow fever virus, Wesselsbron virus, Ilheus virus, Japanese B encephalitis virus, Murray Valley encephalitis virus, St. Louis encephalitis virus, West Nile virus and Dengue hemorrhagic fever virus as well as a Modoc group. Togaviruses comprise Eastern, Western and Venezuelan equine encephalitis virus while fleboviruses, Rift Valley virus. Coltiviruses comprise Colorado thick fever virus.

Keywords: arboviruses, neuropathology, encephalitides, tick-borne encephalitis, Japanese B encephalitis, dengue
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SYMPOSIUM: VIRUS DISEASES. Herpesvirus
Aktualn Neurol 2007, 7 (2), p. 96-107
ABSTRACT

We review here infections of both peripheral and central nervous system caused by herpes viruses. To the most important entities one should classify: herpetic encephalitides caused by Herpes simplex virus type I and II, encephalitides caused by varicella-zoster virus, encephalitis in the course of infectious mononucleosis (the Epstein-Barr virus) and encephalitides caused by cytomegalia wirus and herpes B virus. In particular, we covered herpes viruses infections as complications of AIDS.

Keywords: herpes viruses, encephalitides, neuropathology, herpes zoster, cytomegalia virus
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SYMPOSIUM: VIRUS DISEASES. Paramyxoviruses
Aktualn Neurol 2007, 7 (2), p. 108-114
ABSTRACT

We review here syndromes caused by viruses belonging to Paramyxoviridae family: mumps causing meningoencephalitis and, rarely, ADEM (acute disseminated encephalomyelitis) and measles. Neurological sequelae in the cause of measles comprise acute disseminated measles encephalitis (ADAM), measles inclusion-body encephalitis (MIBE), subacute sclerosing panencephalitis (SSPE) and post-infectious encephalitis (PIE). The sequence of those encephalitides following measles infection is as follows: acute measles encephalitis comes first, follows by MIBE (1-9 months) and SSPE (3-15 years). The measles encephalitis in the course of HIV infection is a separate phenomenon.

Keywords: paramyxoviruses, mumps, measles, subacute sclerosisng panencephalitis, neuropathology
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SYMPOSIUM: VIRUS DISEASES. Poliovirus
Aktualn Neurol 2007, 7 (2), p. 115-118
ABSTRACT

The poliovirus is classified among the family Picornaviridae and genus Enterovirus. Due to intensive vaccinations with Salk and Sabin vaccines, the worldwide polio epidemics belong to the past; the eradication of polio in the Western countries was achieved by 1991. Neuropathologically, the major changes occur in the anterior horn cells of the spinal cord; lesions are also seen in the brain stem, pons and the cerebellum. The cerebral cortex, except for the precentral gyrus, is unaffected. The disease is biphasic. Initially, it is manifested as a typical viral illness with headache and pharyngitis. Following the incubation period lasting from 9-12 days, the temperature rises again; the signs of meningismus, nausea and vomiting, somnolence or agitation are observed. In a few days, signs of flaccid paralysis including respiratory muscles follow. In 25-60% of survivors, the postpolio progressive muscular atrophy, PPMA develops.

Keywords: polio, Picornaviridae, neuropathology, virology, postpolio syndrome
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SYMPOSIUM: VIRUS DISEASES. Rabies
Aktualn Neurol 2007, 7 (2), p. 119-121
ABSTRACT

Rabies is a fatal disease (50 000 death in the third Word countries) caused by a virus from a family Rhabdoviridae (from a Greek noun rhabdos – a rod). A virus, cause rabies, demonstrated a characteristic bullet-like shape. Human beings are infected by rabid animal bite (dogs or foxes); there is a possibility of infection through the aerosols in caves invested by carnivorous bats. The virus is ubiquitous; the exceptions are: Antarctic, the British Isles, Ireland, Island, New Zealand, Hawaii, Bahamas and Bermudas. In the Western countries and the USA, also in Poland, the prevalence of rabies is low (1 case in the USA in 1998 and 4 in 1997), but in countries like India or Mexico, the prevalence is in a range of 3.3/105 and thousand of deaths every year (mainly in India). About 50% of cases of rabies is diagnosed in boys under 15. Neuropathologic study reveals features of encephalitis; cytoplasmic Negri bodies are present within the neurons. 

Keywords: rabies, encephalitides, neuropathology, Rhabdoviridae, Negri bodies
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SYMPOSIUM: VIRUS DISEASES. Progressive multifocal leucoencephalopathy
Aktualn Neurol 2007, 7 (2), p. 122-124
ABSTRACT

Progressive multifocal leucoencephalopathy (PML) is an invariably lethal, progressive demyelinating disease, caused by the JC virus (the term consists of initials of the patient, in whom the virus has been first isolated – John Cunningham), of the Polyomaviridae family. Before, the JC virus was enumerated among the Papovaviridae, a family which includes also papillomaviruses. The JC virus has been isolated from brains of patients with progressive multifocal leucoencephalopathy and is considered the etiologic factor here, although it may also cause renal and upper respiratory tract diseases. Suggestions about viral aetiology of PML appeared as early as the ‘50s, but only ultrastructural studies by Gabrielle Zu Rhein revealed structures identical to virions of polyoma viruses. Microscopic lesions are usually much more pronounced than those visible by naked eye. Most often, these are symmetric, diffuse foci of subcortical demyelination, ranging from microscopic to large, confluent and encompassing most of the white matter in a particular area. Within these foci visible are oligodendrocytes featuring large basophilic nuclei with viral inclusion bodies and hypertrophic, monster astroglial cells. 

Keywords: JC virus, Papovaviridae, progressive multifocal leucoencephalopathy, encephalitis, neuropathology
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SYMPOSIUM: VIRUS DISEASES. Borna disease
Aktualn Neurol 2007, 7 (2), p. 125-126
ABSTRACT

Borna disease (the name stem from a small village in Saxony, Germany where the disease became epidemic in 1895) is caused by atypical virus (Borna disease virus, BDV). BDV is prototypic virus of the family Bornaviridae, within the order Mononegavirales within which viruses of Ebola and Mahrburg, an Rhabdoviridae are also classified. Noteworthy, all attempts to isolate BDV with methods of classical virology failed and the virus was only molecularly cloned in the late eighties of the XX century. BDV occur epidemically in Germany, Switzerland, North America, Japan and Israel. It seems that, analogously to rabies virus, it may infect all the vertebrates including horses, primates, ships, lamas, hippos, cats and cattle but also birds (ostrich). The virus reservoir are probably small rodents. The problem of BDV infection in humans is still open to debate. 

Keywords: viruses, Borna, Rhabdoviridae, encephalitides, neuropathology
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Spinal pain syndrome and headache as initial manifestation of spinal cord tumour – a report of two cases
Aktualn Neurol 2007, 7 (2), p. 127-131
ABSTRACT

Two cases of intraspinal thoracolumbar tumours with meningeal involvement in boys aged 10.5 and 12 years are presented. Medical history of both patients comprised headaches and back pains lasting for some weeks and months before admission. Because of the significant extension of the neoplastic process, one patient was disqualified from tumour resection and was administered with neoadjuvant chemotherapy. The second patient received partial tumour resection and supplementary intense chemotherapy. Both children died of disease progression after 2 and 15 months after first symptoms occurrence, respectively. Autopsy revealed malignant gliomas with extensive meningeal involvement as well as neoplasm dissemination within central nervous system via cerebro-spinal fluid in both cases. Vertebral pain is a rare neurological symptom in children, requiring particular attention and thorough radiological examination. It needs to be stressed that headaches may be also the first symptom of the tumour located within vertebral column. 

Keywords: vertebral pain, spinal cord tumours, malignant gliomas, children
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