NORMAL PRESSURE HYDROCEPHALUS

Normal pressure hydrocephalus, usually seen in older adults, is a completely treatable condition with good result. Unfortunately a good number of these individuals are misdiagnosed as some incurable condition like Alzheimer’s disease and left untreated.

 The brain and spinal cord are surrounded by a clear fluid called cerebrospinal fluid (CSF). This fluid circulates around the brain and spinal cord. An excess of CSF can occur when the natural system for draining and absorbing the extra CSF does not work properly. The ventricles (CSF filled spaces in the centre of the brain) start to enlarge to accommodate the extra fluid and then press on different parts of the brain, causing a number of different symptoms. This condition, called hydrocephalus, causes very high pressure in the brain.

Normal pressure hydrocephalus (NPH) is a type of hydrocephalus that occurs in adults, usually older adults (>60 yrs). It develops slowly over time as the drainage of CSF is blocked gradually, and the excess fluid builds up slowly. This means that the fluid pressure in the brain may not be as high as in other types of hydrocephalus. However, the enlarged ventricles still press on the brain and can cause symptoms.

NPH can occur after head injury, bleeding around the brain (called subarachnoid haemorrhage), stroke, meningitis (infection of the protective membrane around the brain), brain tumours or after surgery on the brain.

Symptoms

At first, the symptoms in normal pressure hydrocephalus are usually very subtle and worsen very gradually. The symptoms are of three types: dementia (reduced intelligence), difficulty in walking and urinary symptoms.

The dementia symptoms include:

• Memory loss
• Speech problems
• pathy (indifference) and withdrawal
• Changes in behavior or mood
• Difficulties with reasoning, paying attention, or judgment.

The walking problems include:

• Unsteadiness,
• Lower limb weakness causing shuffling steps and sudden falls.
• Difficulty in taking the first step, as if feet were stuck to the floor (magnetic gait).
• "Getting stuck" or "freezing" while walking.

The urinary symptoms include:

• Inability to hold urine
• Frequent urination
• Urgency to urinate.

These symptoms can be confused with normal aging and the patient is left untreated but could be due to NPH which is a treatable condition. Any of these problems, or changes in mood or behaviour, warrants a visit to your health care provider. The symptoms of NPH can occur in Alzheimer disease and Parkinson disease. However, the combination of dementia-like symptoms, walking problems, and urinary problems should alert your health care provider to the possibility of NPH. Making the distinction is very important because the treatments for these conditions are quite different. Tests are available that can confirm the diagnosis. At any point in this process, your health care provider may refer you to a specialist in brain disorders (neurologist or neurosurgeon) to complete the evaluation and begin treatment. 

Exams and Tests.

The evaluation for NPH includes a detailed clinical assessment with detailed questions on the symptom followed by detailed physical examination to document your condition. This is necessary to rule out other problems that might cause similar symptoms. The examination will probably include tests of your mental status, such as answering questions and following simple directions Called mini mental status examination). Neuropsychological testing may be performed to document your dementia symptoms.  Neuropsychological testing is the most accurate method of pinpointing and documenting a person's cognitive problems and strengths and helps to give a more accurate diagnosis of the problems thus helping in treatment planning. It assesses cognitive abilities such as memory, attention, orientation to time and place, use of language, and abilities to carry out various tasks and follow instructions. Reasoning, abstract thinking, and problem solving also are tested.

Lab tests:

There is no lab test that confirms the diagnosis of NPH. Any lab tests that are done are probably being done to rule out conditions that might cause similar symptoms. 

Imaging studies

• CT scan of the head.
• MRI of the head.

 Lumbar puncture involves removal of CSF from the area around the spinal cord in the lower back. The CSF pressure is measured, and the fluid that is removed is analyzed for abnormalities that might give a clue as to the problem. Usually, more fluid is removed than is necessary for these tests. The idea behind this is that removal of a large volume of CSF helps relieve symptoms. (This is checked by comparing examination results before and after). This effect usually is only temporary. However, improvement of symptoms with lumbar puncture is commonly interpreted as meaning that a surgical shunt would be helpful in that person.

Treatment.

Normal pressure hydrocephalus generally cannot be cured. It is a long-term condition. However, many people with the condition obtain substantial relief through surgical treatment. For those who are not candidates for surgery, treatment consists of measures to relieve mood and behavioral problems, cope with physical problems such as incontinence and walking difficulties, and maximize physical, mental, and social functioning.

Medical Treatment: No drug or other medical treatment is known to work in NPH.

Surgery: Occasionally the cause of the hydrocephalus can be treated directly through surgery. For example, a brain tumour blocking drainage of the CSF can be removed. In most cases, however, the underlying problem is not known or cannot be treated. The treatment in these cases is a shunt operation. A shunt is a thin tube that is implanted and drains the excess CSF away from the brain and spinal cord. The tube is routed under the skin. The shunt can be inserted either from the ventricles of the brain or the subarachnoid space of the lower spine to the peritoneum from where it is absorbed. A shunt operation is not a cure. It does not treat the underlying cause of NPH. It can, however, relieve the symptoms. The shunt remains in place indefinitely. If properly implanted, the shunt often is not obvious to other people. Most people who undergo a shunt operation have substantial symptom relief. Many surgeons perform a spinal tap before surgery to test whether the symptoms get better with removal of fluid. In some cases, the person is hospitalized for a few days while fluid is drained slowly through a small tube. This is another way of checking whether removing extra fluid will help symptoms.

The earlier the NPH is diagnosed, the better the chances that the surgery will help. In general, people with milder symptoms have better outcomes with this surgery. Like any surgery, the shunt operation can cause complications. Such complications include infection of the shunt and bleeding around the brain. Another operation is sometimes used instead of shunt placement. In endoscopic third ventriculostomy, an endoscope (thin tube with a lighted camera on the end) is used to create a small hole in the floor of the ventricles. The hole provides another way for CSF to drain from the brain.

SPASTICITY

NEW TREATMENT FOR ALCOHOLISM

Alcoholism, also known as alcohol dependence, is a disabling addictive disorder characterised by compulsive and uncontrolled consumption of alcohol despite its negative effects on the drinker's health, relationships, and social standing. The World Heath Organisation estimates that there are 140 million alcoholics worldwide. In our country also the figures are huge and causes like of social, marital, psychological and financial problems.

Worldwide, 76.3 million people suffer from alcohol dependence that accounts for about 1.8 millions deaths a year. Currently following successful detoxification, a combination of pharmacotherapy, psychotherapy and other psychosocial interventions is recommended as standard treatment of alcohol dependence to achieve abstinence. Although these interventions have shown to be significantly effective when compared to placebo or non-treatment, the majority of the addicted does not achieve abstinence and subsequently develop physical and / or psychological complications. They are at increased risk for early death by somatic complications or suicide. It is estimated that alcoholics have a 60 – 120 times greater suicide risk compared to non-psychiatric patients. In addition to the physical and psychosocial complications of alcoholism, about one half of the violence- related crimes are committed under the influence of alcohol. In a recent German study of the long-term course of alcoholism after in-patient treatment, only 40 % remained abstinent after 16 years. Of those who died during follow-up, 73 % did not remain abstinent

Treatment of alcoholism has been mainly medical. There are many drugs as well as other measures like counseling which benefit a good number of patients. But the relapse rate is very high. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) in the U.S. reported that approximately 90% of alcoholics are likely to experience at least one relapse over the 4-year period following treatment due to craving for alcohol. Craving for alcohol is an appetitive urge, similar to hunger, that varies in intensity and is characterized by withdrawal-like symptoms. The symptoms are elicited by internal and external cues that evoke memory of the euphoric effects of alcohol and of the discomfort of withdrawal.

Nucleus accumbens (NAcc) is an area of the brain which has long been suspected to be the reward centre of our brain. The NAcc in each half of the brain is thought to be responsible for the memory associated with pleasures, which lead to an intricate reward system in our brains and bodies. Also it is believed to be the source of motivation and drive. Since the NAcc is thought to be pivotal to rewards and pleasures, many believe it is also tied in to addictions, ranging from alcohol and drugs, to sex and food.

Figure on the left shows the nucleus accumbens and connections whereas the figure on the right shows the reward circuit.

There is now enough proof that the NAcc is linked to the rewarding of human behaviours which is controlled by releasing chemicals in the brain called neurotransmitters. The two main neurotransmitters involved are dopamine and serotonin. Serotonin is known as the neurotransmitter that gives the body the impression of satisfaction and hence the body no longer desires the stimulant that was provided initially. Conversely, dopamine is the neurotransmitter that increases the desire for that stimulant. Studies have shown that defective dopamine function in the NAcc correlated with alcohol craving, which was associated with a high relapse risk.

Deep brain simulation (DBS) is now an established surgical procedure for many diseases like Parkinsonism, various types of pain syndromes etc. DBS has the advantage of being adjustable, with stimulation parameters such as amplitude, frequency, width of the stimulating pulse, and the location being under control of the clinician. Moreover, the procedure is nondestructive and carries a very low operative risk, making it a very attractive treatment option.

Many recent studies have shown that DBS of the NAcc is a very good option for alcoholism. Kuhn et al treated a 54-year-old patient with severe anxiety disorder complicated by secondary depressive disorder and alcohol dependency by bilateral DBS of the NAcc with the aim to alleviate anxiety and depression. Whereas the patient experienced only a moderate reduction of his anxiety disorder and depression, he showed a remarkable reduction of alcohol intake such that 1 year after surgery he consumed alcohol only occasionally. Muller et al reported three patients with alcoholism who received deep brain stimulation. In the one-year follow-up period, two remained abstinent, while one showed a remarkable reduction of days while drinking and none had any significant adverse effects. In all three patients, craving behaviour disappeared immediately after the activation of deep brain stimulation in the nucleus accumbens. None of the patients reported unwanted somatic or psychological side effects after DBS. All patients reported that their lives had changed enormously and that they became able to experience pleasurable feelings about common things of live without substance abuse.

There have also been a few animal studies on DBS of NAcc in alcoholism. A recent animal study carried out in rats found that DBS of the NAcc significantly attenuated the reinstatement of drug seeking. DBS to the NAcc in addiction appears to be specific both in terms of the stimulation location and in terms of the attenuation of “wanting” a specific substance. Another recent article reported that deep brain stimulation (DBS) in the nucleus accumbens (NAcc) decreases alcohol intake in alcohol-preferring (P) rats after each animal has established a stable, large alcohol intake and after P rats with an established intake have been deprived of alcohol for 4–6 weeks. They found that Deep brain stimulation in the NAcc, as compared with a period of sham-DBS treatment in the same animals, acutely decreased alcohol preference. Furthermore, alcohol consumption and preference were significantly reduced in the DBS group compared with the sham treatment group during the first 24 hours that alcohol was made available after a period of forced abstinence. Another similar study has shown the positive effects of nucleus accumbens stimulation rats addicted to morphine.

NEW TREATMENT FOR ISCHAEMIC HEART DISEASE (REFRACTORY ANGINA)

Even as the treatment of ischaemic heart disease has improved significantly, there remains some patients who are not well controlled with maximum possible drugs and who are not good candidates for either coronary artery bypass grafting or percutaneous transluminal angioplasties. This is especially so as the life expectancy is increasing. These patients are having refractory angina. Refractory angina is defined as a chronic condition caused by clinically established reversible myocardial ischemia in the presence of coronary artery disease, which cannot be adequately controlled by a combination of best medical therapy, angioplasty or coronary artery bypass operations. The presence of reversible myocardial ischaemia should be clinically established to be the cause of the symptoms. Chronic angina is defined as angina with duration of more than 3 months. The incidence of refractory angina is around 30 per million inhabitants per year; other estimates are 2.5–5% of all coronary angiography procedures.

Most cases of ischaemic heart disease can be treated with drugs, angioplasties or bypass grafting and the results are very good, both having stood the test of time. Angioplasty and bypass grafting causes revascularisation i.e. restoring and improving the blood supply to the heart. But some patients do not benefit from any of these. All of us know somebody who has undergone an angioplasty or bypass surgery and have not benefited by this procedure.

Then the question that arises is why revascularisation (restoring the blood supply) is not possible in some cases? The reasons include the following:

• Unsuitable anatomy, such as diffuse coronary sclerosis (diffuse blocking of the blood vessels), often with well-preserved left ventricular function. Sometimes called end-stage angina.
• One or several previous CABGs and/or PTCAs which exclude further benefit or possibility of further revascularisation.  >
• Lack of adequate graft material.
• Impaired left ventricular function in patients with previous CABG and/or PTCA.
• Extracardiac diseases which increase perioperative and postoperative morbidity/ mortality, such as general arteriosclerotic disease, renal insufficiency, carotid stenosis and pulmonary disease.
• Age — often in combination with the above mentioned factors.

What is Neurostimulation? How does it work in angina?

Neurostimulation is low-voltage electrical stimulation to the spinal cord that inhibits the sensation of pain. The sensation of stimulation is perceived as paraesthesia (tingling). The goal of neurostimulation is to create maximal neurostimulation-induced paraesthesia to cover the patient’s pain pattern. Spinal cord stimulation (SCS) may alleviate angina by two ways:

• Direct pain-inhibiting effect
• Affecting underlying ischaemia, as shown by:

• Reduced ST segment depression
• Increased time to ST segment depression
• Reduced total ischaemic burden during Holter monitoring.

The picture above shows how the spinal cord stimulator is put in place at C7 –T2 levels. The picture below shows the spinal cord stimulator and the pulse generator (battery).

Indications for Spinal cord stimulation in refractory angina pectoris:

• Stable angina pectoris with activities of daily living severely limited by angina (NYHA/CCS 3–4)
• Insufficient improvement in functional capacity or pain control despite optimal medical treatment
• No foreseen prognostic benefit from revascularization
• Documented CAD (or Syndrome X)
• Patient able to understand and comply with the treatment.

Patients with chronic refractory angina pectoris are usually 70 years or more and are predominantly male. They have a history of long term (more than 10 years) coronary artery disease especially three vessel disease. They do have history of previous myocardial infarction(s) and history of previous revascularisation procedure(s). They usually will have good left ventricular function and with no serious arrhythmias.

Studies have shown that Neurostimulation for angina pectoris does not:

• Deprive or conceal the patient of a warning signal during myocardial infarction
• Adversely affect mortality rate
• Increase the number of ischaemic episodes or show a rebound effect
• Demonstrate complication rates unlike other SCS applications.

The ESBY study compared Electrical Stim vs. CABG in Severe Angina Pectoris

• 104 refractory angina patients randomized to SCS (53) or CABG (51) – the ESBY Study
• Cardiac mortality significantly lower in SCS group (1) compared to CABG group (7)
• Neurostimulation and CABG were equivalent methods in terms of symptom relief
• CABG was superior during exercise testing but cerebrovascular events less with SCS.
• It was concluded that SCS may be a therapeutic alternative for patients with increased risk of surgical complications.

A study on long-term outcome regarding quality of life and survival in patients in ESBY study showed that

Quality of life improved significantly 6 months after spinal cord stimulation and coronary artery bypass grafting, The results were consistent after 4·8 years. The 5-year mortality was 27·9%.

There were no significant differences between the groups.

Both methods can be considered as effective treatment options for patients with severe angina. SCS should be considered in patients with increased surgical risks and estimated to have no prognostic benefits from CABG.

A prospective, controlled, long-term follow-up study on the role of spinal cord stimulator in Cardiac syndrome X

• Cardiac syndrome X is a condition where younger patients develop angina but the angiogram is normal.
• 19 pts with CSX with refractory angina who underwent SCS; controll 9 comparable patients with CSX who refused SCS treatment Median (range) follow-up of 36 (15-82) months.
• At baseline no difference in clinical characteristics and angina status. All indicators like angina episode frequency, duration & short-acting nitrate use, functional status, QOL, Exercise tolerance, exercise-induced angina and ST segment changes improved significantly at follow-up in SCS group but not in controls.
• CONCLUSIONS: Data show that SCS can be a valid form of treatment for long-term control of angina episodes in patients with refractory CSX.

Many studies have shown that spinal cord stimulator causes

• Fewer hospital admissions: post CABG = 0.97 per patient year vs. post SCS = 0.27 per pt. year (p=0.02) and Reduced average length of stay: post CABG 8.3 days vs. post SCS 2.6 days (p=0.04) leading to significant savings (upto £ 2,051 per patient year).
• ~50% reduced frequency of angina episodes, with reduced nitroglycerin intake.
• 20-25% improvement in exercise capacity, with evidence of less ST-segment depression.
• Increased functional status, as measured by a 1 to 2 class reduction in NYHA or CCS scores with improved Quality of Life.
• Reduction in nitrate & morphine consumption.
• Neurostimulation produces the following benefits when measured by exercise stress testing: Increased exercise capacity, Increased time to onset of angina, Reduced ST-segment depression.

Despite advanced and sophisticated medical and surgical procedures, a large number of patients suffer from chronic refractory angina pectoris. Spinal cord stimulation (SCS) seems to be the most promising for these patients. Controlled studies suggest SCS provides symptomatic relief equivalent to surgical or endovascular procedures, but with a lower rate of complications and re-hospitalisation. Similarly, SCS proved cost effective compared to medical as well as surgical or endovascular approaches in a comparable group of patients. This technique is still met with reluctance by the medical community. Reasons for this disinclination may be related to incomplete understanding of the mechanism of action of SCS and the fact that SCS refers to the modulation of neuroendocrine parameters rather than to revascularization, which is currently the dominant treatment paradigm in coronary artery disease.

A systematic review and meta-analysis of the use of spinal cord stimulation (SCS) in the management of refractory angina was done (BMC Cardiovascular diseases 2009; 9:13-26).

Seven RCTs were identified in a total of 270 refractory angina patients. The outcomes of SCS were found to be similar when directly compared to CABG and percutaneous myocardial laser revascularisation. The healthcare costs of SCS appeared to be lower than CABG at 2-years follow up. Conclusion: SCS appears to be an effective and safe treatment option in the management of refractory angina patients and of similar efficacy and safety to PMR, a potential alternative treatment.

So spinal cord stimulation is a suitable and comfortable alternative for patients who are not expected to have a good result as a result of angioplasties or bypass surgeries. The surgery takes about 1 hour and patient is discharged by next day; the programming of the device is done on an out patient basis.. The risks associated with a major surgery (bypass grafting) do not exist. So next time a dear one of yours undergoes a coronary angiogram and you are advised an angioplasty or bypass surgery, ask your cardiologist about the extent of the disease and the expected results. Always keep spinal cord stimulation as an alternative is specific cases (as per indications above).

PARKINSONISM: DIAGNOSIS AND TREATMENT

Parkinson disease (Parkinson's disease, PD) is a progressive neurodegenerative disorder associated with a loss of dopaminergic nigrostriatal neurons. Dopamine is a nerve chemical which is very essential for all movements. In Parkinson’s disease the amount of dopamine gets reduced (like insulin in diabetes). Parkinson disease is recognized as one of the most common neurological disorders, affecting approximately 1% of individuals older than 60 years. The incidence has been estimated to be 4.5-21 cases per 100,000 population per year. Estimates of Parkinson disease prevalence range from 18-328 per 100,000 population, with most studies yielding a prevalence of approximately 120 per 100,000. Studies have shown that in India the incidence is bound to double in ten years.

Symptoms : The most common symptoms include resting tremor (shaking), rigidity (stiffness), bradykinesia (poverty of movement) and postural instability (frequent falls). Onset in Parkinson disease is typically asymmetric, with the most common initial finding being an asymmetric resting tremor in an upper extremity. About 20% of patients first experience clumsiness in one hand (difficulty in writing) but over time progressive bradykinesia, rigidity, and gait difficulty set in. Sleep disturbances are common.

The characteristic Parkinson disease tremor is present and most prominent with the limb at rest. It is described as pill rolling tremor. Rigidity refers to an increase in resistance to passive movement about a joint. Bradykinesia refers to slowness of movement but also includes a paucity of spontaneous movements and decreased amplitude of movement. Bradykinesia is also expressed as micrographia (small handwriting), hypomimia (decreased facial expression), decreased blink rate, and hypophonia (soft speech).Postural instability refers to imbalance and loss of righting reflexes. Its emergence is an important milestone, because it is poorly amenable to treatment and a common source of disability in late disease. Patients may experience freezing when starting to walk (start-hesitation), during turning, or while crossing a threshold, such as going through a doorway. Dementia generally occurs late in Parkinson disease and affects 15-30% of patients. Short-term memory and visuospatial function may be impaired, but aphasia is not present.

Causes : Most cases of idiopathic Parkinson disease are believed to be due to a combination of genetic and environmental factors. At both ends of the spectrum are rare cases that appear to be due solely to one or the other. A recent hypothesis suggests that Parkinson disease is caused by abnormalities of the proteosome system, which is responsible for clearing abnormal proteins. Parkinsonism can be caused by a variety of degenerative disorders, as well as toxins, infections, and vascular or structural lesions. Parkinsonism also can be induced by medications that block dopamine receptors (eg, neuroleptics, antiemetics) or deplete intraneuronal dopamine stores (eg, reserpine, tetrabenazine).

Investigations : No laboratory biomarkers exist for Parkinson disease. Magnetic resonance imaging (MRI) and computed tomography (CT) scan are usually unremarkable or may show age specific changes in Parkinson disease. Positron emission tomography (PET) and single photon emission CT (SPECT) are also not needed for routine clinical diagnosis in patients with a typical presentation. However they may be useful in diagnostic dilemmas.

Treatment : Most cases of Parkinsonism especially in the initial phases are well controlled on medications. The goal of medical management of Parkinson disease is to provide control of signs and symptoms for as long as possible while minimizing adverse effects. Medications usually provide good symptomatic control of motor signs for 4-6 years. After this, disability progresses despite best medical management, and many patients develop long-term motor complications including fluctuations and dyskinesia. Additional causes of disability in late disease include postural instability (balance difficulty) and dementia.

The various classes of drugs used in Parkinsonism include :

1. Dopamine prodrugs (Levodopa or combinations)

2. Anticholinergic drugs (trihexiphendyl)

3. Dopamine agonists (bromocriptine, pergolide, pramipexole, ropinirole).

4. MAO-B inhibitors (selegiline, rasagiline, Amantidine)

5.COMT inhibitors (entacapone)

6. Anti hallucination drugs (quetiapine, clozapine) in case of hallucinations.

Drug management is very effective in all patients for some time. But over time they become less effective or may even cause side effects. It is in these situations that that surgery can be offered. Surgery is of three types :

Deep brain stimulation (DBS)

Lesioning

Neural transplants.

Of these, lesioning and neural transplants have not given consistent good results. So deep brain stimulation is now the treatment of choice. Deep brain stimulation (DBS) for Parkinsonism involves stimulating the subthalamic nucleus (STN) with electrodes.

Indications for DBS in Parkinsonism

1. Advanced Parkinson’s disease with disabling motor fluctuations and dyskinesias refractory to drug changes.

2. Levodopa induced dyskinesias.

3. Medication refractory symptoms with significant disability and interference with daily activities including writing, feeding, dressing, etc.

4. No significant cognitive impairment and no major psychological problems.

5. 10 years after diagnosis.

6. Patients understand and accept therapy.

The DBS electrode and the battery For good results the four contact points of the electrode needs to be in the STN.
Coronal cross section of brain showing the basal ganglia (green and blue) in the left and the subthalamic nucleus (yellow) and the substansia nigra (red)

STN DBS involved inserting the electrodes shown above into the subthalamic nucleus. This procedure is done using the stereotactic frame and under local anaesthesia. STN DBS for Parkinsonism usually resolves tremor, dyskinesias, pain and hallucinations. Symptoms which are improved by drug therapy are maximally improved with surgery. Tremor improves by 80%-100%, slowness (Bradykinesia) by 50%-60%, stiffness (Rigidity) by 50%-70%, gait, freezing, and balance by 50%, dyskinesias and dystonia (drug induced) by 80%- 90% and motor fluctuations are virtually eliminated. Independence and quality of life are substantially improved. Complications are very rare and include haemorrhage (2-3%), Infection (1 -3%), mechanical hardware breakage (1-5%) and cognitive decline (2%).

Postoperative Xrays of one case is shown here.

Patient who underwent microvascular decompression for trigeminal neuralgia

CHRONIC PAIN