Wednesday, January 2, 2008

Central Nervous System and Infections Associated with It

By Sudipa Sarkar
The Central Nervous System — Structure & Function
The Nervous System is characterized by the complex network of neurons that are responsible for all bodily functions both at conscious as well as unconscious level. This nervous system is divided into two portions – the Central Nervous System (CNS) and Peripheral Nervous System (PNS). As its name implies it is central to our system – the most important nervous system structure that governs almost all the physical and mental activities. The Central Nervous System or CNS comprises of two essential parts of our body – the brain and the spinal cord. The CNS is situated within the dorsal cavity, including the brain in cranial cavity and the spinal chord in spinal cavity. The CNS is wrapped by the meninges, that of the brain by skull and for the spinal chord it is with the spinal cavity. The brain is subdivided into prosencephalon, mesencephalon and rhombencephalon. They are commonly known as forebrain, midbrain and hindbrain respectively. Again forebrain comprises of diencephalons which in turn is subdivided into thalamus and hypothalamus. The hypothalamus is an essential part of our brain which influences different kinds of hormonal functions as well as governs emotional behaviour, visceral activities, food intake pattern, sex drive, sleeping pattern and the production of antidiuretic hormone (ADH) and oxytocin in association with the limbic system. On the other hand, thalamus consists of several numbers of nuclei that are responsible to receive stimuli from different sensory organs like eye, ear or skin and it is then in return bypass information in both inward and outward directions. Depending on the functional pattern, the brain is subdivided into 4 parts –
• The cerebrum
• The diencephalons
• The cerebellum and
• The brain stem

The cerebrum divides the brain into left and right hemisphere along with a communication channel, corpus callosum. This area of the brain is responsible for language, conscious thoughts, hearing, somatosensory functions, personality development and memory.

The diencephalons, consisting of hypothalamus, thalamus and epithalamus, form the central part of the brain. It plays the major role in maintaining a balance in the system – known as homeostasis. The cerebellum is at the rear part of the brain. This is responsible for controlling the balance, posture and coordination. The brain stem basically connects the cerebrum and cerebellum to the spinal chord. It is responsible for visual and auditory reflexes, controlling of swallowing, breathing, digestion, and heartbeat.
The spinal chord is actually a continuation of body stem and is responsible for carrying message between the CNS and rest of the body and it arbitrates numerous spinal reflexes such as the knee-jerk reflex.

Therefore, it is clear that without the proper functioning of central nervous system we are unable to perform any kind of actions, including basic level like moving or hearing to the most advanced one like thinking, feeling pain or remembering.

Infections of Central Nervous System (CNS)

In general, the central nervous system is well protected against infection. Still, under some circumstances it may get affected by various kinds of infection, including viral, bacterial, fungal or protozoan in nature. The infections caused by those infectious microorganisms are due to either by direct penetration in the CNS or through bloodstream. The people suffering from AIDS, Cancer, diabetes, alcoholism or substance abuse disorder or who use steroid for a prolonged period are highly susceptible to CNS infections more than normal people having normal immune defense system. Once affected, the infections in the central nervous system may become fatal. Infection in central nervous system caused by virus may include meningitis, encephalitis, poliomyelitis, slow virus infections, acquired immune deficiency syndrome (AIDS), and post-infectious syndromes. Bacterial infection in CNS may cause the onset of meningitis, brain abscess, subdural and epidural abscesses, neurosyphillis, tuberculosis or leprosy. Fungal infection in general causes meningitis or meningoencephalitis, brain abscess, or spinal epidural infection. For the protozoan infection, it may lead to toxoplasmosis, malaria or amoebic infection.

Viral Infection

The virus caused infection in central nervous system is prevalent among infants rather than adults, but not a rare case indeed. In general, the viruses cause the infection in the central nervous system includes arboviruses, coxsackieviruses, echoviruses, enteroviruses and herpesviruses. They cause infection primarily at the base level affecting meninges which results into meningitis. These may affect the brain causing encephalitis. In its most complex fashion, it may affect both the meninges and brain and result into meningoencephalitis. Primarily virus affect the CNS in two ways –

They directly affect and destroy the cell during acute illness.
They may influence and affect the immune response of the body after recovery from acute illness – may result parainfectious or postinfectious encephalitis including the diseases like measles, chicken pox or rubella.

In case of infants and toddlers, the main symptoms for viral infection of central nervous system may include an initial onset of fever accompanied by irritable behavior, reluctant about eating, vomiting. While in movement, the infant suffering from meningitis may cry more than usual as the discomfort in meninges is raised by movement. Infants suffering from encephalitis show a symptom of seizures or bizarre movements, which may worsen to lethargic, then comatose and eventually die if the infection turns to be more severe in time. In case of postinfectious encephalomyelitis, the victim may develop many neurologic problems depending on the area of brain damage, which may lead to weakness on the area of movement or function of arm, leg or body, visionary or hearing loss, mental retardation or recurring seizures.

The diagnosis of virus caused CNS infection primarily includes the following technique:-

1. Basic observation: Doctors are always concerned about the possibility of development of meningitis or encephalitis in newborns or older infants with high fever accompanied by irritation and unusual behavior pattern.
2. Spinal tap: In this technique infants undergo for lumbar puncture to collect cerebrospinal fluid for laboratory analysis. If it is the case of viral infection, then no bacteria are found and the numbers of lymphocytes in blood cells get increased.
3. Immunologic tests: This technique is used to detect antibodies against viruses in the sample of cerebrospinal fluid, but it is a time-consuming method.
4. Polymerase Chain Reaction (PCR): This method is used to identify the presence of micro-organisms such as herpesviruses and enteroviruses.
5. Electroencephalography: This technique is used to diagnose encephalitis due to herpesvirus by testing brain waves.
6. Brain Biopsy: This method is rarely done to measure the presence of herpesvirus as the cause of infection.

The prognosis and treatment of the infection of CNS caused by virus is vastly dependent on the type of infection. If the level of infection is not so serious or is detected almost on the onset of the disease, the infant may recover soon. But if there is severity or it has been occurred for a prolonged period of time without sufficient care, it may lead to fatality, leading either death or permanent neurologic disability of some kind. Infants need supportive care like warmth, proper diet, and plenty amount of fluids along with medicinal treatment. Still today, the antiviral drugs are not very much effective for the treatment of CNS infection, however, infections due to herpes simplex virus can be treated with acyclovir (zovirax) using intravenously.

Bacterial Infection

The bacterial infection in central nervous system can affect people at any age or sex. In case of bacterial infection, it may affect the system primarily in two ways –
Abscesses and
Empyemas

Abscesses are characterized by fixed boundaries with a specific shape and size, whereas empyemas are not like that. The bacterial CNS infection is categorized by their location of appearance of the disease, such as a spinal epidural abscess is situated on the top of the dura mater, whereas a cranial subdural empyema is located in between the dura mater and the arachnoid. In case of intracranial abscesses prompt recognition and immediate action are needed. These type of abscesses are sub-categorized into three modes –
Extradural
Subdural
Intracerebral
Delay in recognition as well as treatment may result grave, causing the victim to have permanent severe disability or die.

In most of the cases of infections in central nervous system caused by bacteria are due to either inoculation from penetrating wound – surgical procedure for example, or spread from adjacent infective portions – chronic sinus or middle ear infection extending beyond its initial state, or blood borne spread from distant focus – lung abscess. For local focus of infection, the bacteria spread through diploeic veins. The abscesses usually develops in sub-cortical white matter adjacent to septic focus. In the case of haematogenous abscesses, it may be multiple in number.

The general symptoms include headaches, stiff neck, back pains, fever, sensory loss, increased weakness and vomiting in association with a progressive blurring of conscious experience. This may be combined with seizures, paralysis or coma in severe condition. The care of concern needs to take immediately on the onset of increased focal signs of neurological abscesses.

The diagnosis for the bacterial infection may include the followings:

Basic observation: The patient with fever, severe headaches, stiff neck problem along with focal signs may be suspected for a victim of CNS infection and thus need to take proper care by specialists.
Blood test: Blood tests can be done to diagnose the presence, but futile to identify the location of infection.
MRI scan: This scan of both brain and spinal chord is very effective for exact diagnosis.
Spinal tap: The lumbar puncture analysis of cerebrospinal fluid is indeed very helpful in the case of epidural abscess, but may lead to potential fatality for subdural empyema.

In case of treatment, there are two processes involved – antibiotic therapy and / or surgery. Surgery is not a very common incidence in the treatment of CNS infection due to bacteria unless the condition becomes beyond control of drug therapy alone. However, the surgery process provides two potential benefits associated with it –
a) It offers immediate relief from the pressures developed in the area of brain or spinal chord;
b) It allows to collect the bacterial specimen which eventually helps to make the necessary alteration in the drug therapy suitable for specific kinds of bacterial infection.

The fatality rate for bacterial central nervous system infection varies from 10% to 40%. In some cases, the victims of this type of infection may develop speech problem, partial paralysis or seizures causing from permanent CNS damage whatsoever. But if the care is taken promptly and on time, the individual may experience a complete recovery.

Recent research studies revealed the existence of a molecular version of an anchor, which permits the penetration of bacteria into the CNS. Hence by blocking the molecules anchoring ability in blood stream, it may well be used in the development of effective drug for the treatment of bacterial meningitis.

Fungal Infection

In the case of fungal infection in central nervous system, it is reported that it can be developed with the presence of viral infection as well. Fungal infection in CNS is basically characterized by the fungal infection in the mycoses of the brain, spinal cord, and meninges resulting in encephalitis; meningitis, brain abscess; and epidural abscess. There are certain types of fungi which are able to produce infection in immunologically normal system, but there are some others, identified as opportunistic pathogens, affect primarily in immunocompromised individuals like those persons having Acquired Immunodeficiency Syndrome (AIDS).

In order to find out the causes behind the onset and development of fungal infection on central nervous system, the first and foremost reason identified is that the more weakened the immune system is for an individual, more susceptible he is for fungal infection. The primary pathogen that lead to the development of the disease may include aspergillosis, blastomycosis, cryptococcus, coccidiomycosis, candidiasis, histoplasma, and sporotrichosis as the potential to cause meningitis due to fungal infection in CNS.

The study on the treatment of central nervous system fungal infections conducted by Punnee Pitisuttithum, Ricardo Negroni, et al, it was found that the oral medication of posaconazole is safe and effective for the subjects already exposed to triazole antifungal agent and with persistent fungal infections or bigoted of standard antifugal therapy. Study on the determination of efficacy of Voriconazole conducted by Stefan Schwartz, Markus Ruhnke, et. al. emphasized that Voriconazole is more efficient in persistent aspergillosis, in contrast with amphotericin B. and to other antifungal drugs as well. Another study conducted by K V Clemons, E Brummer, and D A Stevens declared that the use of interleukin-12 alone and in combination with common antifungal therapy in experimental cryptococcosis provides an efficient outcome.

Protozoan Infection

The protozoan infection in the central nervous system may lead to fatality if not arrested on time. Protozoa are uni-celled organisms. Infection in CNS due to protozoa may lead to extreme fatality on time. the protozoan Trypanosoma cruzi is responsible for Chagas' disease, which is characterized by an active circulation of parasites in the blood and multiply in several cell types, especially muscle cells. A life-long chronic phase follows the acute phase causing severe dysfunctional condition in central nervous system as well as in peripheral nervous system. In case of youngsters, the acute phase become more severe, with the frequent occurrence of meningoencephalitis.

For the infection by Trypanosoma, the CNS is usually affected in the advanced level of the infection caused into the system, hence, increasing the rate of fatality to higher extent. At that point, the general symptoms found include sleeping-sickness, apathy, mental dullness, disturbed coordination, tremors, paralysis, and convulsions. In the progression of the disease, the sleeping-sickness problem also increases, which eventually leads to coma and death.

However, the use of arsenical drugs is prevalent, but toxicity is common as well. The medication like suramin, pentamidine, and Berenil are considered as successful if the disease is diagnosed in its early stages.
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