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Central Nervous System - Disease Topic Overview

The Central Nervous System

The central nervous system (CNS) is composed of the brain, brain stem, cerebellum and spinal cord. At a cellular level the CNS is made up of highly specialised cells called neurones, whose electrical excitability can transmit signals in the form of action potentials. In addition to neurones the CNS also contain astrocytes, oligodendrocytes, microglia and ependymal cells.¹

There are many diseases that affect the CNS, including epilepsy, schizophrenia, Alzheimer’s disease and mood disorders (depression, anxiety, bipolar disorder).

Epilepsy is a neurological disease that is indiscriminate of age; affecting approximately 50 million people worldwide.² The seizures, caused by abnormal neuronal excitation, can take four main forms; simple partial seizures, complex partial seizures, absence seizure (petit mal) or tonic-clonic seizures (grand mal).

Alzheimer’s Disease is primarily a disease of the elderly, with the risk of developing this debilitating disease increasing exponentially with age (doubling every 4.5 years).³ It is caused by the formation of plaques in the cerebral cortex, this results in the symptoms of memory loss and confusion. Currently there is no cure, although the development of the disease can be slowed through pharmacological intervention.⁴

Mental health disease is a global issue with schizophrenia and depression affecting 26 million and 151 million people worldwide respectively.⁵ There is still a stigma that surrounds these disorders. Treatment is typically through counselling and treatment with a selective serotonin reuptake inhibitor (SSRI). SSRIs act to inhibit the reuptake of serotonin by pre-synaptic neurones causing an increased concentration of this neurotransmitter at the synaptic cleft.⁴

1. Tortora GJ. et al. Principles of Anatomy and Physiology. Wiley. 2006 : 404-411
2. WHO. Epilepsy Atlas 2005. WHO. 2005 : 1-15
2. Mathers C. et al. Global burden of dementia in the year 2000: summary of methods and data sources. WHO. Geneva. 2000.
4. Martini FH. et al. Fundamentals of Anatomy and Physiology. Pearson International. 2009 ; 8 :554-555
5. Funk M. et al. Mental Health and Development: Targeting People With Mental Health Conditions as a Vulnerable Group. WHO Geneva. 2010 : 34

Alzheimer's Disease
Alzheimer's disease(AD) is a progressive, neurodegenerative disease which will affect most of us at one point in time, and it’s prevalence increases with age.

In the early stages in particular, dementia is often difficult to diagnose, since many symptoms are not recognized as such or are trivialized by the patient. 20% of actual dementia cases are reported to be incorrectly diagnosed as a different disease.

In early dementia the symptoms of Alzheimer’s disease include memory loss, disorientation and confusion. These symptoms are caused by the loss of neurons and worsen with continuous neurodegeneration. The pathology of dementia is not solely the result of a cholinergic deficit. It is known that, chronically and pathologically elevated glutamate concentrations play an important role.

In general two main groups of dementia can be distinguished, requiring different types of treatment:
- Cerebro-organic (primary) forms of dementia
- Non-cerebro-organic (secondary) forms of dementia
Depending on the stage of the disease, clinical symptoms of varying intensity dominate. With the progression of AD, treatment is aimed particularly at improving and stabilizing personal everyday functions, so as to keep patients independent for as long as possible.

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Alzheimer's disease (AD) is a progressive, neurodegenerative disease which will affect most of us at one point in time - either directly (as the prevalence is expected to quadruple over the next 50 years) or indirectly through the suffering of a loved one.

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Migraine
Migraine is a common neurological disorder characterised by recurrent episodes of headache pain with associated symptoms including nausea, vomiting, sensitivity to light and sound, and, in a minority of patients, transient neurological symptoms, with visual disturbances being the most common.

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Migraine is a severe, episodic disorder with freedom from symptoms between attacks. Attacks are characterised by transient focal neurological symptoms, headache, or both.

Correctly diagnosing a migraine headache enables prompt and appropriate therapeutic intervention, reducing the distress and pain experienced by patients. An incorrect diagnosis of migraine can have a significant effect on both migraineurs and their families.

Several sets of guidelines have been developed to assist in the diagnosis of migraine.

Among migraineurs, understanding and assessing the severity and disability of a patient’s illness is an important step in ascertaining their treatment needs.

The Migraine Disability Assessment (MIDAS) questionnaire is a self-administered form that assesses the impact that migraine has on a patient’s work and social life. It can be used prior to and at the time of an initial consultation and throughout treatment to monitor the patient’s progress.

The use of a headache diary, which allows patients to record events that play a role in their headaches, is also a useful tool that may aid the physician in the diagnosis of migraine.

Despite the availability of migraine-specific medications such as the triptans, which are effective and well tolerated for the acute treatment of migraine, many migraineurs lapse from physician care before being prescribed an effective treatment.

It is advised that users of this resource consult their local treatment guidelines before initiating any treatment programme for a patient with migraine. Once migraine is diagnosed, patients and physicians should decide together how best to treat acute attacks and whether to use preventive medications.

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Multiple Sclerosis
The hallmark of multiple sclerosis (MS) as revealed by magnetic resonance imaging (MRI) is the white matter plaque, which represents an area of demyelination and axonal loss. MS can produce lesions throughout the central nervous system (CNS).

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The hallmark of multiple sclerosis (MS) as revealed by magnetic resonance imaging (MRI) is the white matter plaque, which represents an area of demyelination and axonal loss.

MS can produce lesions throughout the central nervous system (CNS), but certain sites appear to be especially vulnerable, such as the optic nerve, brain stem, spinal cord and periventricular regions. Involvement is often bilateral and symmetrical. Lesions are broadly divided into two types: acute and chronic.

Acute lesions are inflammatory in nature and exhibit infiltration by T-lymphocytes, B-lymphocytes and macrophages, which may be filled with myelin debris from the breakdown of myelin sheaths. Proliferation of astrocytes is also usually evident, accompanied by oligodendrocyte loss.

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Parkinson's Disease
Parkinson's disease (PD) is a progressive, degenerative disorder of the central nervous system, which causes increasing disability over time. PD predominantly occurs in people over the age of 50 and is the commonest neurodegenerative disorder after Alzheimer's disease that a physician will encounter.

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Parkinson's disease (PD) is a degenerative disorder of the central nervous system characterized by the clinically asymmetric onset of resting tremor, bradykinesia, rigidity and postural instability.^1-3

Parkinson's disease (PD) is the second most common neurodegenerative disorder, after Alzheimer's disease.^{1, 2}

The most recent and comprehensive clinical guidelines for the diagnosis and management of Parkinson's disease (PD) in primary and secondary care have been compiled by the UK National Institute for Health and Clinical Excellence (NICE).⁴

A diagnosis of Parkinson's disease (PD) can be difficult as, in common with other central nervous system degenerative disorders, PD begins insidiously.

The severity of Parkinson's disease (PD) can be assessed using a number of rating scales, assessing patients' motor function, activities of daily living (ADL), mental status, dependency and complications of therapy.

It is important that patients with Parkinson's disease (PD) are treated as soon as a full diagnosis has been made; several studies have shown that patients who receive effective symptomatic treatment earlier in the course of their disease fare significantly better clinically than patients who delay their treatment.^5-7

It is not possible to identify a universal first-choice drug therapy for patients with early PD.⁸ In Established/advanced Parkinson's disease⁹ therapy choices need to be re-evaluated.

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References

1. de Lau, L.M. and M.M. Breteler, Epidemiology of Parkinson's disease. Lancet Neurol, 2006. 5(6): p. 525-35.
2. Schapira, A.H., Science, medicine, and the future: Parkinson's disease. BMJ, 1999. 318(7179): p. 311-4.
3. Guttman, M., S.J. Kish, and Y. Furukawa, Current concepts in the diagnosis and management of Parkinson's disease. CMAJ, 2003. 168(3): p. 293-301.
4. NICE, N.I.f.H.a.C.E., NICE clinical guideline: Parkinson's disease: diagnosis and management in primary and secondary care. 2006.
5. Schapira, A.H. and J. Obeso, Timing of treatment initiation in Parkinson's disease: a need for reappraisal? Ann Neurol, 2006. 59(3): p. 559-62.
6. Poewe, W.H. and G.K. Wenning, The natural history of Parkinson's disease. Neurology, 1996. 47(6 Suppl 3): p. S146-52.
7. Rajput, A.H., Levodopa prolongs life expectancy and is non-toxic to substantia nigra. Parkinsonism Relat Disord, 2001. 8(2): p. 95-100.
8. Horstink, M., et al., Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies and the Movement Disorder Society-European Section. Part I: early (uncomplicated) Parkinson's disease. Eur J Neurol, 2006a. 13(11): p. 1170-85.
9. Horstink, M., et al., Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies (EFNS) and the Movement Disorder Society-European Section (MDS-ES). Part II: late (complicated) Parkinson's disease. Eur J Neurol, 2006b. 13(11): p. 1186-202.

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Soft Tissue Sarcoma
Soft Tissue Sarcomas (STS) are malignant (cancerous) tumors that develop in tissues which connect, support, or surround other structures and organs of the body. Muscles, tendons (bands of fiber that connect muscles to bones), fibrous tissues, fat, blood vessels, nerves, and synovial tissues are types of soft tissue.

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Soft Tissue Sarcomas (STS) are malignant (cancerous) tumors that develop in tissues which connect, support, or surround other structures and organs of the body. Muscles, tendons (bands of fiber that connect muscles to bones), fibrous tissues, fat, blood vessels, nerves, and synovial tissues are types of soft tissue.

Soft tissue sarcomas are grouped together because they share certain microscopic characteristics, have similar symptoms, and are generally treated in similar ways¹. They are usually named for the type of tissue in which they begin.

Every year approximately 13,000 new cases of soft tissue sarcomas are diagnosed in adults and children in Europe. The 5-year survival rate for patients with soft tissue sarcoma is around 90% if the cancer is detected in early phases and before it has spread. However, the 5-year survival rate is 10% to 15% for sarcomas with metastasis.

Management of STS depends on the stage of disease and histological subtype². Surgery is the mainstay of treatment for patients with localised disease and is often curative. However, as recurrence is likely to occur when tumour cells remain after surgery, adjuvant radiotherapy is often also considered, especially for patients with intermediate or high-grade tumours. Radiotherapy is also often administered for patients in whom surgery is inappropriate or who decline surgery.²

There are a number of Associations and Organisations across Europe who strive to inform others of this disease as well as offer help and support to those affected or to those who know and want to help those suffering.

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References

1. Cormier JN, Pollock RE. Soft tissue sarcomas. CA: A Cancer Journal for Clinicians 2004; 54(2):94–109.
2. Clark MA, Fisher C et al. (2005) “Soft-tissue sarcomas in adults.” N Engl JMed 353(7): 701–11.

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Latest Multi Media

An Overview of Brain Surgery and the Current Understanding of Brain Function

Central Nervous System Drug Data - A-Z English

Drug Updates

Aricept Tablets

ARICEPT tablets are indicated for the symptomatic treatment of mild to moderately severe Alzheimer's dementia.

Kemadrin 5 mg Tablets

Kemadrin is indicated for the treatment and symptomatic relief of all forms of Parkinson's disease e.

Parvolex 200 mg/ml Concentrate for Solution for Infusion

For the treatment of paracetamol overdosage.

Latest Drug News

Tysabri(Biogen IDEC/Elan) enters Phase III ASCEND trial for Secondary Progressive Multiple Sclerosis - 29-01-2012

Biogen Idec and Elan Corporation, have announced a global Phase IIIb study, ASCEND, that is being conducted to evaluate the effectiveness of Tysabri as a treatment for secondary-progressive multiple sclerosis (SPMS). According to the National Multiple Sclerosis Society, approximately half of all people initially diagnosed with relapsing-remitting Multiple Sclerosis (RRMS) - the most common form of Multiple Sclerosis (MS) - will transition to SPMS within 19 years. Patients with RRMS typically experience unpredictable relapses; the time between relapses is characterized by full or partial recovery and a lack of disease progression. SPMS is characterized by a steady progression of nerve damage, symptoms and disability, but the exact reasons for the progression are unknown. The potential for greater disease burden in SPMS typically includes decreased mobility, impaired activities of daily living, loss of independence and reduced quality of life. The primary endpoint is to investigate whether treatment with Tysabri slows the accumulation of disability not related to relapses in subjects with SPMS.

Rebif (Merck Serono) is EU approved for Early Multiple Sclerosis - 26-01-2012

The European Commission has approved an extended indication for Rebif (interferon beta-1a) from Merck Serono, allowing its use in patients with early Multiple Sclerosis, in line with an earlier recommendation by the CHMP. It recommended that 44 micrograms of Rebif three times weekly should be given to patients who have experienced a single demyelinating event, an early sign of Multiple Sclerosis, and who are at high risk of developing the disease.

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Women With Epilepsy: Pregnancy Outcomes and Deliveries (WEPOD)

This is a three-center prospective case-control study to examine the patterns of fertility among women with epilepsy (WWE) compared to an age-matched group of women without epilepsy (WWoE).

Childhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study

The purpose of this study is to determine the best initial treatment for childhood absence epilepsy.

Latest Journal Publications

Journal of the neurological sciences

A 73-year-old man had episodic encephalopathy, ataxia and neuropathy. Symptoms largely resolved but adenopathy later lead to the diagnosis of a low-grade follicular lymphoma. The neurological symptoms soon recurred with new pontine calcifications identified by computed tomography. Brain biopsy revealed microvascular endothelial cell nuclear changes. Electron microscopy identified small polymorphic bacteria without a cell wall and with terminal and attachment organelles within endothelial cells and clustered in some microvascular lumina. Immunostaining was positive for Mycoplasma pneumoniae and convalescent serum enzyme immunoassay was positive for M. pneumoniae IgG. The patient again recovered and he was neurologically stable 33months after the initial episode. The ultrastructural findings of the bacterial cells are distinctive of some mycoplasmal species when compared to other small bacteria. Mycoplasma-like organisms are reported in four autopsied patients who had chronic encephalopathy, movement disorders, and some of the same light- and electron-microscopic findings in the brain as our patient. Direct neuroinvasion by Mycoplasma species has been suggested, while anatomic observations in our patient and in the four autopsy cases show microvascular invasion but not parenchymal invasion. Most mycoplasmal encephalitis may be immune-mediated. The frequency of neurovascular invasion is not known. It may be rare and it may persist.

Journal of Experimental Child Psychology

Speech perception of four phonetic categories (voicing, place, manner, and nasality) was investigated in children with specific language impairment (SLI) (n = 20) and age-matched controls (n = 19) in quiet and various noise conditions using an AXB two-alternative forced-choice paradigm. Children with SLI exhibited robust speech perception deficits in silence, stationary noise, and amplitude-modulated noise. Comparable deficits were obtained for fast, intermediate, and slow modulation rates, and this speaks against the various temporal processing accounts of SLI. Children with SLI exhibited normal “masking release” effects (i.e., better performance in fluctuating noise than in stationary noise), again suggesting relatively spared spectral and temporal auditory resolution. In terms of phonetic categories, voicing was more affected than place, manner, or nasality. The specific nature of this voicing deficit is hard to explain with general processing impairments in attention or memory. Finally, speech perception in noise correlated with an oral language component but not with either a memory or IQ component, and it accounted for unique variance beyond IQ and low-level auditory perception. In sum, poor speech perception seems to be one of the primary deficits in children with SLI that might explain poor phonological development, impaired word production, and poor word comprehension.

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TEMSO study for Aubagio in Multiple Sclerosis is published in NEJM Central Nervous System Page

The pivotal Phase III TEMSO study with investigational once-daily oral medication Aubagio (teriflunomide) from Sanofi/Genzyme is published in The New England Journal of Medicine (NEJM). Results showed that teriflunomide at the 14mg dosage significantly reduced the annual relapse rate, reduced disability progressions and improved several magnetic resonance imaging (MRI) measures of disease activity, including new or worsening brain lesions in relapsing, remitting Multiple Sclerosis. Teriflunomide has a well-characterized safety profile, with a similar proportion of trial participants reporting adverse events compared to placebo. Teriflunomide has been filed with the FDA in August of 2011 and the EMA filing is expected in the first quarter of 2012. see Randomized Trial of Oral Teriflunomide for Relapsing Multiple Sclerosis Paul O'Connor, M.D., et al for the TEMSO Trial Group N Engl J Med 2011; 365:1293-1303 October 6, 2011.

Tysabri shows benefits in Multiple Sclerosis patients Central Nervous System Page

Patients with Multiple Sclerosis who take anti-inflammatory Tysabri (natalizumab), from Biogen and Elan, for two years showed a reduced risk of experiencing at least one relapse (at 2 years this was reduced by 40%). The study also showed that the number of patients whose disability progressed in the time interval was reduced by 25%. In addition, MRI scans showed evidence that treatment with Tysabri reduced disease activity. Treatment also created some side effects including limb swelling, rigors, vaginal inflammation and menstrual disorders and 2 patients treated with Tysabri for more than 2 years developed Progressive Multifocal Leukoencephalopathy, a rare and often fatal viral disease. In light of this, the researchers recommend further studies. The review was published in The Cochrane Database of Systematic Reviews: "Natalizumab for relapsing remitting multiple sclerosis" by Eugenio Pucci et al. Issue 105 OCT 2011.Tysabri is approved in the USA and EU.

Lemtrada and Aubagio trials to report at ECTRIMS/ACTRIMS congress Central Nervous System Page

Genzyme/Sanofi will report more than 20 abstracts at ECTRIMS/ACTRIMS congress. Data will include Phase III results of Lemtrada(alemutuzumab) and Aubagio ( oral teriflunomide) in relapsing remitting Multiple Sclerosis (MS) including CARE-MS 1 study comparing Lemtrada and Rebif (interferon beta 1-a) in relapsing remitting MS and five year extension of TEMSO study of oral Aubagio (Poster 924) and efficacy of Aubagio (Poster 438) and long term results for Lemtrada CARE-MS Phase II trial (Poster 928) and four year efficacy of Lemtrada in MS (Poster 931). Lemtrada is being developed by Genzyme/Sanofi in the USA and Bayer HealthCare in the EU.