Category: Top level

It is a premature aging of the brain progressing rapidly to extreme loss of mental power or memory loss due to death of brain cells. Alzheimer disease was originally characterized in middle-aged people,and similar deterioration in elderly individuals is technically senile dementia of the Alzheimer type,though it is frequently just called Alzheimer disease. Both genetic and environmental factors can contribute to the etiology of the disease. In these cases,the disease is caused by mutations in genes for the amyloid precursor protein on chromosome 21, presenilin 1 on chromosome 14, presenilin 2 on chromosome 1. It is transmitted in an autosomal dominant mode,so offspring in the same generation have a 50/50 chance of developing familial Alzheimer disease if one of their parents is affected.

SIGN&SYMPTOMS

Memory loss is the key symptom of Alzheimer disease. People with Alzheimer disease may also have;

• Repeat statements and questions over and over.
• Forget conversations, appointments or events, and not remember them later.
• Eventually forget the names of family members and everyday objects.
• Have trouble finding the right words to identify objects, express thoughts or take part in conversations.
• Alzheimer’s disease causes difficulty concentrating and thinking, especially about abstract concepts such as numbers.
• The ability to make reasonable decisions and judgements in everyday situations will decline.
• Changes in personality and behavior.

• Brain changes that occur in Alzheimer’s disease can affect moods and behaviors. problems may include the following;
• Depression
• Apathy
• Social withdrawal
• Mood swings
• Distrust in others
• Irritability and aggressiveness
• Changes in sleeping habits
• Wandering
• Loss of inhibitions
• Delusions, such as believing sometimes has been stolen.

CAUSES

The cause of Alzheimer disease is unknown. Scientists know that in Alzheimer disease there is large build-up of proteins called amyloid within brain cells. These proteins occur normally, but not yet understand why they build up in large amounts. The disease process can go on for many years without symptoms, but as more and more proteins form brain cells,the cells lose their ability to function and eventually die. This causes the affected parts of the brain to shrink.

Recent studies

• Recent studies found that the symptoms of the disease appears after age of 60 and the risk increases with age.
• Younger people may get Alzheimer’s disease, but it is less common.
• Annually there were 2 new diagnoses per 1000 people ages 65 to 75.
• 11 new diagnoses per 1000 people ages 75 to 85.
• 37 new diagnoses per 1000 people ages 85 and above.
• The number of people living with the disease doubles every 5 years beyond age 65.
• This number is projected to nearly triple i.e 14 million people by year 2060.
• Although the prevalence of the disease appears to be higher in women,this may be due to their longer life span as the incidence rates are similar for men and women. Alzheimer disease plus the other forms of senile dementia are the major medical problem.
• Drugs used to block the production of Beta-amyloid proteins are under development also attempts are under way to develop vaccines that would allow the body’s immune system to produce antibodies to attack these proteins.

Drugs and treatments

The use of acetylcholinesterase inhibitors such as; Donepezil,Galantamine, Rivastigmine,Tacrine. In early stages of the disease increase the availability of acetylcholine in the synaptic cleft. This class of drugs has shown some promise in ameliorating global cognitive dysfunction,but not learning and memory impairments in these patients. These drugs also delay the worsening of symptoms for upto 12 months in about 50% of the cases studied. Memantine (an NMDA receptor antagonist) prevents glutamate-induced excitotoxicity in the brain and is used to treat moderate to severe Alzheimer disease. It delays but does not prevent worsening of symptoms. Like loss of memory and confusion,in some patients.

Parkinson’s disease is also called shaking palsy,was first described by James Parkinson in 1817.Parkinson’s disease occurs in elderly people due to idiopathic degeneration of Nigrostriatal system of dopaminergic neurons. There is a steady loss of dopamine and dopamine receptors with age in the basal ganglia in normal individuals, however it is markedly precipitated in individuals developing Parkinson’s disease.

Parkinson’s disease has both hypokinetic and hyperkinetic features. Parkinson disease is the first disease identified as being due to deficiency in a specific Neurotransmitter. It results from the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The fibers to the part of the striatum are most severely affected.

The hypokinetic features of Parkinson disease are akinesia and Bradykinesia. The hyperkinetic features are cogwheel rigidity and tremor at rest.

There are 7-10 million people worldwide in whom Parkinson disease has been diagnosed. The disease is 1.5 times more prevalent in men then in women. parkinsonism occurs in sporadic idiopathic form in many middle aged and elderly individuals and one of the most common Neurodegenerative diseases. It is estimated to occur in 1-2% of individuals over age of 65. Dopaminergic neurons and dopamine receptor are steadily lost with age in the basal ganglia in healthy individuals, and an acceleration of these losses apparently precipitates parkinsonism. Symptoms appear when 60-80% of the Nigrostriatal dopaminergic neurons degenerate.

Sign & Symptoms

• There are three main symptoms;
• Tremor: shaking, which usually begins in the hand or arm and is more likely to occur when the limb is relaxed and resting.
• Slowest of movement (Bradykinesia).
• Muscle stiffness (Rigidity).

• OTHER PHYSICAL SYMPTOMS

• Balance problems.
• Loss of sense of smell.
• Nerve pain.
• Problems with peeing.
• Constipation.
• Erectile dysfunction.
• Sexual dysfunction.
• Dizziness,blurred vision.
• Excessive sweating.
• Swallowing difficulties.
• Excessive production of saliva(drooling).
• Insomnia.

•MENTAL SYMPTOMS

• Depression & Anxiety.
• Mild cognitive impairment.
• Dementia(visual hallucinations).

TREATMENT

• There is no cure for Parkinson disease, and drug therapies are designed to treat the symptoms.
• Sinemet, a combination of levodopa (L- dopa) and carbidopa, is the most commonly used drug for the treatment of Parkinson disease.
• The addition of carbidopa to levodopa increases its effectiveness and prevents the conversion of L-dopa to dopamine in the periphery and thus reduces some of the adverse side effects of levodopa, which includes; Nausea,vomit,and cardiac rhythm disturbances.
• Dopamine agonists, including apomorphine, bromocriptine,pramipexole and ropinirole,have also proven effective in some patients with Parkinson disease.
• Entacapone combination of L-dopa and cathechol-o-methyltransferase(COMT) inhibitor,are another class of drugs used to treat the disease.
• Drug dopamine is not used because it cannot cross the blood brain barrier.
• L-dopa in low doses diminishes rigidity and in high doses reduces tremors.

• Surgical destruction of the globus pallidus or ventrolateral nucleus of thalamus can also reform the symptoms of Parkinson’s disease by restoring the output balance towards normal.

Pheochromocytoma are catecholamine producing tumors derived from the sympathetic or parasympathetic nervous system. The diagnosis of Pheochromocytomas provides a potentially correctable cause of hypertension, and their removal can prevent hypertensive crises that can be lethal.

EPIDEMIOLOGY

Pheochromocytoma is estimated to occur in 2-7 out of 1 million persons per year. The mean age at diagnosis is about 40 years, although the tumors can occur from early childhood until late life. The “Rule of tens” States that about 10% are bilateral, 10% are extra-adrenal, 10% are malignant, 10% are found in asymptomatic patient and 10% are hereditary.

PATHOGENESIS

The name Pheochromocytoma reflects the black coloured staining caused by chromaffin oxidation of catecholamines. A variety of Nomenclature have been used to describe these tumors, but most clinicians use the term Pheochromocytoma to describe symptomatic catecholamine producing tumors.

SIGN & SYMPTOMS

In an earlier studies,blood pressure anomalies were associated with the discovery of Pheochromocytoma in 50% of cases,while headache and palpitations were found in 25% of patients. Pheochromocytoma is typically found with a diverse set of symptoms which may include;

• Anxiety and panic attacks. • Polydypsia. • Polyuria. • Hyperglycemia. • Constipation. • Weight loss. • Visual blurring. • Chest and abdominal pain. • Pallor. • Heat intolerance. • Orthostatic hypotension. • Erythrocytosis. • Tachycardia. • Dilated cardiomyopathy.

DIAGNOSIS

The diagnosis is based on documentation of catecholamine excess by biochemical testing and localization of the tumor by imaging. Both are of equal importance,although measurement of catecholamines is traditionally the first step. High levels of vaniyllylmandelic acid is excreted in urine.

TREATMENT

•Once the diagnosis of a Pheochromocytoma is made,appropriate pre operative medical management is necessary to reduce the risk for peri operative complications. •Complete removal of tumor is the ultimate therapeutic goal. Pre operative patient preparation is essential for safe surgery. Alpha adrenoceptor antagonists,dihydropyridine calcium channel receptor blockers,the tyrosine hydroxylase inhibitor alpha- methyltyrosine, and the competitive alpha & beta receptor blocking drug labetalol have all been successfully used in an oral form for the pre operative treatment. Alpha- adrenergic blockers ( phenotype zamine) should be initiated at relatively low doses (5-10mg po three times per day) and increased as tolerated every few days. Adequate alpha- blockade generally requires 10-14days,with a typical final dose of 20-30mg phenoxybenzamine three times per day. During surgical manipulation of the tumor, massive catecholamine release may occur, which can exceed the normal plasma concentration by > 1000 times. This can result in hypertensive crisis, cardiac arrhythmias, cerebral vascular accident, myocardial infarction or ischemia,pulmonary edema,and multi organ failure.

AIM

The main aim of pharmacological management is to prevent the severe hypotension that can result immediately following removal of the tumor and to abolish or reduce the potentially lethal swings in blood pressure that can occur during induction of an anesthetic and surgical manipulation of the tumor. Stabilization of blood pressure is achieved by the use of a single antihypertensive agent or combination of antihypertensive agents preopertively and intraoperatively to counteract excessive catecholamine adrenergic activity,volume expansion with I.V fluid is achieved, and inotropic support after excision of the Pheochromocytoma if required. There are currently no randomized prospective trials to establish the optimal pre operative pharmacological management of Pheochromocytoma. As a result, there is no clear consensus regarding the drug of choice.