Dr. Siddharth Kharkar

What causes Epilepsy? We have previously defined a seizure as follows: A Seizure is a brief, uncontrolled surge of electricity resembling an electrical storm. A seizure is an electrical storm inside the brain. (Read more here: What is a seizure?) and Epilepsy as follows: Epilepsy is a tendency of the brain to have Unprovoked seizures. If your brain keeps on having seizures, then doctors conclude it has a TENDENCY to have seizures. This tendency is called Epilepsy. (Read more here: What is Epilepsy?) But, what causes the Brain to develop this increased tendency? Is Epilepsy something that you are born with? Is it something that happens due to injury to your Brain? Let us talk about these causes. Is there a single cause for Epilepsy? No. The cause for Epilepsy is different in different people. Epilepsy may be caused by Abnormal Development of our bodies and Brain before we are born, or by injuries to our Brain after birth. For the sake of understanding, allow me to divide the causes into 5 groups: Abnormal Development – producing abnormal brain cells Abnormal Development – causing chaotic brain structure Abnormal Development – causing chemical (metabolic) problems Brain injury due to incidents after birth Auto-Immunity The first 3 categories are due to abnormal genes. As we start to know more and more about seizures, we are beginning to identify more and more gene abnormalities that can cause Epilepsy. E.g. We now know that most cases of “Dravet Syndrome” are caused by SCN1A gene abnormalities which in turn produce a problem with sodium channels on cells (Mechanism 1). Mechanism 1: Abnormal Development – producing abnormal brain cells Our Brain is made up of millions of minute cells. Each one of our cells has little tunnels called “Channels”. These tunnels act as gatekeepers. They can let substances such as potassium and Sodium into the cell, and can also throw these substances out of the cell. Abnormal tunnels in the walls of cells can cause Epilepsy. A problem with the “Channels” on the cell is called a “Channelo-Pathy”. The word “pathy” means disorder. If there is a problem with one of these channels (Channelo-pathy), the cell can become excitable. Most commonly, the problem is with the channel for Sodium. For example, if there is a problem with the channel that regulates Sodium, too much Sodium can enter the cell, and the cell can start throwing small surges of electricity. A lot of cells throwing minute surges may cause a HUGE SURGE of electricity in the Brain – a Seizure. We are discovering that many of our patients have Epilepsy due to a Channelopathy. We are discovering new channelopathies every year. Have a look at the short list below – this is just to illustrate the concept and not for memorization. If you’re interested, you can see a more comprehensive list by clicking here (Spillane et al.). Substance Affected Gene Epilepsy Syndrome Sodium SCN1A Dravet Syndrome Sodium SCN2A Benign Familial Infantile Seizures Potassium KCNQ2 & KCNQ3 Benign Familial Neonatal Convulsions Potassium KCNT1 Malignant Migratory Partial Seizures of Infancy Calcium CACNA1A Childhood Absence Epilepsy Chloride/Calcium Channels GABRA1, EFHC1, CACNB3, CLCN2 & others Juvenile Myoclonic Epilepsy Acetylcholine CHRNA2, CHRNA4, CHRNB2 Autosomal Dominant Frontal Lobe Epilepsy Here is an excellent paper that describes Epilepsy genes causing channelopathy [Bartolini et al 2020]. Mechanism 2: Abnormal Development – causing chaotic brain structure The outer surface of the Brain is called the “Cortex”. The Cortex consists of 3-6 sheets of cells placed on top of each other, like a set of bedsheets on top of each other. The outer surface is also folded, like bedsheets with a lot of creases. These folds are called “Gyri”. Below the Cortex and well separated from it is a bunch of wires, called the “White Matter.” https://commons.wikimedia.org/wiki/File:Cerebral_cortex,_side_view.svg This exquisite arrangement is critical for proper brain functioning. If this arrangement does not correctly form before birth, abnormal electrical connections can be created, like two electrical wires crisscrossing each other. The resulting short circuit can cause electrical sparks/surges in that part. These surges can then spread throughout the Brain producing a HUGE SURGE – a seizure. Let us briefly discuss some of these problems with the structure of the Brain: 1.Lissencehaply / Pachygyria: “Lissen” means Smooth & “Cephaly” refers to the Brain = Smooth Brain Paychy means “few” & “Gyri” are the folds of the Cortex = Few Folds https://upload.wikimedia.org/wikipedia/commons/9/9d/Lissencephaly.jpg In both these conditions, the number of folds of the Cortex (the wrinkles) are reduced. Therefore the surface of the Brain looks smoother than usual. 2. PolyMicroGyria: “Poly” means many, “Micro” means small, & “Gyri” are the folds of Cortex = Many small folds In this condition, there are too many folds of the Cortex! Therefore the surface of the Brain looks exceptionally wrinkled. 3. Focal Cortical Dysplasia & Nodular Heterotopia: While the Brain is developing, the cells of the Cortex may not form properly and get arranged haphazardly. Usually, this involves only a part of the Brain (Focal) rather than the entire Brain. The Latin word for abnormal formation is “Dysplasia”.  Therefore this disease is called “Focal Cortical Dysplasia” or FCD for short. Frequently these abnormal cells get stuck in the mass of cells called the “White matter” instead of reaching the Cortex. They formed nodules below the Cortex. Heterotopia in Latin means “Abnormal Movement”. Therefore, this disease is called “Nodular Heterotopia.” As can be imagined,  “Focal Cortical Dysplasia” & “Nodular Heterotopia” commonly occur together, but each one can also happen separately. 4. Tuberous Sclerosis & Cortical Tubers: Tuberous Sclerosis is a disease in which patients have white patches on the skin and nail and eye abnormalities, in addition to seizures. In this disease, the Brain has multiple abnormalities. One of them is strange blobs of cells in the Cortex with scarring and calcification which produces large bumps on the surface of the Brain. these are called “Cortical Tubers.” 5. Mesial Temporal Sclerosis: The temporal lobes are the part of the Brain below the ears. Sometimes, the inner side of this part develops scarring. In Latin, the inner side is called

Shuffling gait means a walking pattern, in which a person drags his/her feet while walking. Shuffling gait is defined as a walking pattern in which thefoot is still moving when it hits the ground. Some people call it “Festinating gait“. But, shuffling gait and Festinating gait are different. Festinating gait is a walking pattern with rapid, small steps as if the person is going to fall over. You can see a video of shuffling gait, and a video of festinating gait below. The most common cause of both is Parkinson’s disease. But there are also other causes of shuffling gait such as hydrocephalus. The treatment of shuffling gait depends on its cause. Hello! I am Dr Siddharth Kharkar, a Neurologist in Thane, India and a Neurologist in Mumbai, India. I provide Parkinson’s treatment in India and am an Epilepsy specialist in India. I provide Epilepsy surgery in India at Mumbai & Parkinson’s surgery in India. Let us learn more about these patterns of gait. What is the meaning of Shuffling gait? Let us think about a fictional person, Sue. Sue has a normal gait. Sue starts walking. Sue first lifts one foot up. Then he moves that foot forward. After the foot is adequately in front, Sue stops moving it forward. She then places the foot down on the ground. Sue can do this very rapidly, and walk very fast. Usually, we walk like Sue. We do not shuffle. == Shuffling gait means a peculiar way of walking, in which the foot is still moving when it hits the ground. Let us look at another person, Mary. Mary does not lift the foot high off the ground. She moves it forward slowly. Even before he/she moves it forward adequately, it is time to put the foot down! And so she does so. This causes Mary to shuffle while walking. This is the meaning of a “shuffling gait”. See this sample video of bradykinesia posted by a Russian doctor on youtube: Festinating gait verus Shuffling gait Festinating gait and shuffling gait are slightly different terms. Festinating gait happens when the person bends forwards while walking. Let us look at a third person – Michael. Michael bends forwards at all times – sitting, standing & even while walking. Now, Michael starts to walk. But he immediately feels like he will fall forwards on his face. He takes a quick short step forward to avoid falling. Saved! But again, immediately, he again feels like he will fall forwards. So he takes another quick, short step. And so on… This is called a Festinating gait. Note that these movements are rapid. It is different than the slow shuffling gait seen in Parkinson’s disease. You can see an example of Festinating gait in the video below (youtube – Ms. Kosutzka): Thus, Festinating gait happens when the patient bends forward while walking. He/she then takes rapid, small steps while walking to avoid falling forwards. Further reading: Gait festination in parkinsonism: introduction of two phenotypes – Jorik Nonnekes, Journal of Neurology 2019; 266(2): 426–430.It is not essential to read this paper. This paper talks about the controversies regarding these two terms. It is fascinating, but is difficult to read for a non-medical audience. Shuffling gait causes The most common cause of shuffling gait is Parkinson’s disease. In Parkinson’s disease, the patient becomes slow. So, the gait is a slow shuffling gait. Treatment can dramatically improve this slow shuffling. Some other conditions can mimic shuffling gait. If someone has very painful knee arthritis they cannot lift their feet high off the ground. Their gait may be mistaken for a shuffling gait. 5 causes of Shuffling gait that are not Parkinson’s disease Alzheimer’s disease – the person might “forget how to walk”. This is called “Gait Apraxia”. Hydrocephalus – Excessive water inside the head Vascular disease – obstructions to blood flow to the brain, causing small strokes. Severe unsteadiness – due to problems with the balance system of the body. The person feels like he is going to fall all the time. Hence, he takes small, shuffling steps instead of boldly stepping forward (“Cautious gait”). Parkinson’s Plus syndromes [Click here for reading more] Sometimes, the gait seen in these diseases is extremely difficultif not impossible to differentiate from the shuffling gait of Parkinson’s disease. For example, here is a video posted by the hydrocephalus association of America. This patient has Normal Pressure Hydrocephalus (NPH), and NOT Parkinson’s disease. As you can see, the gait looks very similar to Parkinson’s disease. Thus, NPH can mimic Parkinson’s disease. So, it is critical to look for other features of the “Parkinsonian gait” before making a diagnosis. For example, watch the video above again. Notice how there is no slowness of the upper part of the body. Other features of the gait in Parkinson’s disease are described below. What is Parkinson’s gait? The term GAIT in medicine includes all body movements while walking. In Parkinson’s changes in the movements of other body parts are also seen. Gait changes seen in Parkinson’s disease Head is bent forward Body is bent forward The person may take some time to start walking (“Freezing”). Once he or she starts walking: The normal swinging of arms while walking is reduced. The chest and stomach appear “stiff” while walking Walking becomes slow Shuffling gait and/or festinating gait may be seen There might be unsteadiness while walking The person might “Freeze” when he/she has to turn. This also happens when walking through doorways or around obstacles. You can notice these changes in the videos below. In the early stages of Parkinson’s, these changes may be very subtle. That is why it is so easy to miss the diagnosis of Parkinson’s disease. Here is an excellent video demonstrating these symptoms. This video has been made by Lancet, a leading medical journal. Treatment of shuffling gait of Parkinson’s The treatment of shuffling gait depends on its cause. The most common cause is Parkinson’s disease. In Parkinson’s disease, the brain has a deficiency of the chemical called Dopamine. Levodopa is an oral medication. Once it goes to the brain, it gets converted into dopamine! This can

What is “Syncope”? “Syncope” means loss of consciousness due to decreased blood supply to the brain. “Syncope” is the most important and common Seizure Mimic. Some events look almost precisely like seizures but are not seizures. These events are called “Seizure Mimics”, and may be mistaken for seizures. There is NO electrical surge in the brain with any of these “Seizure Mimics”. If an episode of  Syncope is mistaken for a Seizure, two things happen: Unnecessary treatment with anti-epileptics, and lack of treatment for the “true” condition (e.g. cardiac arrhythmia). Which problems cause “Syncope”? Lets quickly summarize how blood goes to the brain: The heart receives oxygenated blood from the lungs. It pumps this blood to the brain through large blood vessels in the neck. The heart takes oxygenated blood from the lungs and pumps it to the brain. 4 Groups of problems can cause Syncope: 4 Problems Causing Syncope Heart problems Overactivity of the vagal nerve A sudden drop in BP on standing up (Orthostatic Hypotension) Problems with blood vessels going to the brain Which heart problems can cause Syncope? If the heart has become weak (for example due to multiple heart attacks) and not able to pump enough blood, the patient may occasionally lose consciousness. This cause is not very common. A weak heart can cause episodes of unconciousness (syncope) More common is an obstruction to blood flow in the heart.Valves in the heart usually keep blood moving in only one direction. They can open and close as needed. Sometimes the heart valves (especially a valve called the Aortic Valve) may become damaged and incapable of opening completely – this decreases blood flow to the brain. Sometimes, the heart wall around the Aortic Valve may become thickened producing the same effect – this condition is called “Hypertrophic Sub-Aortic Stenosis”.An echocardiogram quickly & easily detects these structural problems. Valve problems in the heart may obstruct the flow of blood and cause episodes of unconciousness (syncope) A straightforward problem to miss is Cardiac Arrhythmia. Usually, the heart beats regularly, almost like a clock. But if the wiring system of the heart develops problems, it may have episodes where it suddenly stops beating or starts beating very rapidly without pumping any blood. This condition is called a cardiac Arrhythmia (A = lack of – rhythm).Since these rhythm problems occur only once in a while, a single ECG may miss them. Therefore, an EEG machine that is stuck to your chest and records your heart rhythm for many days (A Holter Monitor) may be required. Newer devices called External Loop Recorders (ELDs) can record your heart rhythms for many months at one time!You may require a pacemaker if you have a severe cardiac arrhythmia. An irregularly beating heart can cause unconciousness (syncope) What do you mean by overactivity of the Vagal Nerve? The vagal nerve is a long nerve from the brain to the heart. When it is active, it can decrease the heart rate. The vagus nerve is an extremely long nerve that goes to many organs, including the heart. If something overstimulates the vagal nerve, it can become overactive. It then causes the heart to become very, very slow. This causes decreased blood flow to the brain and leads to loss of consciousness. It is easy to identify the precipitant that caused the vagus nerve overactivity. The following is a list of such precipitants. Only the first one is common: Intense Emotion or Pain: Being startled, the sight of blood, intense fear etc Choking on something. Rarely swallowing very cold or hot food can cause Syncope. Massaging the neck or wearing a very tight collar (which leads to stimulation of sensors called carotid bodies which are connected to the vagus nerve) Passing urine (Micturition Syncope) Rarely: Laughing hard and Orgasms What can cause a sudden drop in Blood Pressure on standing (Orthostatic Hypotension)? Meaning of Orthostatic Hypotension Ortho = Straight,  Statikos = to stand Hypo = Low, Tension = Pressure Meaning: Low Pressure on Standing Straight A drop in blood pressure may cause unconciousness (syncope) When we stand up suddenly, blood tends to pool in our legs, and our brain tends to get less blood. To prevent this, the blood vessels in our legs contract and our heart beats faster. If these things don’t happen, our heart pumps less blood, and our blood pressure drops. This may cause us to lose consciousness. When some people stand up suddenly, their brain does not get enough blood. This is alled Postural or orthostatic hypotension. A sudden and large drop in our Blood Pressure on getting up suddenly is called “Orthostatic Hypotension”. During your office visit, the doctor may check your BP when you are lying down and then ask you to get up suddenly. While you are standing, he/she will check your BP two more times. If your upper (systolic) BP drops by more than 20 units, or your lower (diastolic) BP drops by more than 10 units, its likely that your events are due to Orthostatic Hypotension. In some cases, an advanced test called a “Tilt Table Test” confirm the diagnosis. A tilt table test is used to diagnose postural hypotension What can cause this drop in BP? There are many causes! It is difficult to remember all of these causes, but I list them here so that you can understand the monumental task facing your doctor and are patient while he goes through a series of tests to find the exact cause of your orthostatic hypotension: Causes of Orthostatic Hypotension Examples Brain Problems – Parkinson’s disease and its sisters like MSA – As part of normal ageing Nerve problems (Neuropathy) Damage to nerves controlling the heart & blood vessels due to: – Alcoholism – Diabetes – B12 deficiency – HIV – Many others… Heart Problems – Cardiac failure – Valve problems Dehydration Not enough fluid in the body due to: – Drinking very little water – Diarrhoea or vomiting Hormonal Problems – Low functioning of the Adrenals (Addison’s) – Low thyroid levels

Is it possible to mistake another kind of event for a seizure? Yes! It is important to remember that many other conditions may look just like seizures, but are not seizures. These are the “Seizure Mimics”. Seizure mimics look like seizures, but are NOT seizures. There is NO electrical surge in the brain with any of these “Seizure Mimics”. Hence, they should not be treated with anti-surge / anti-seizure / anti-epileptic medications. But identifying them is very important since some of them (e.g. Sandifer syndrome) may need a different kind of treatment. Here, we will discuss seizure mimics that are unique to children, that is seizure mimics that occur in children, but not in adults. Some seizure mimics may happen in both adults AND children – these are discussed in another article. If you are interested in seizure mimics, make sure you read that article as well. How do we maintain our balance? The 6 mimics below are probably the most important to know. These 6 mimics may be initially misdiagnosed as seizures, occasionally even by very competent doctors. Seizure mimics can confuse the most experienced doctors! The list below is not comprehensive. I have not included more common episodes like migraine and tics, because these are usually simple to distinguish from seizures. Also, as mentioned above, make sure you read the separate article about Seizure Mimics that may happen in adults AND children to get the full picture. [Seizure mimics in adults and children]. Seizure Mimics in Children Benign neonatal sleep myoclonus Breath-holding spells Sandifer syndrome Masturbation Shuddering attacks Benign paroxysmal torticollis & Benign paroxysmal tonic upgaze Great! Can I skip the visit to the doctor? Of course not! You could miss a seizure disorder. For example: Breath-holding spells & Tonic seizures look similar. Shuddering attacks and Infantile Spasms (a variety of seizure) can look very similar and so on. Do not diagnose your child with one of these seizure mimics without further confirmation from a doctor. Use this information only as a starting point for a detailed conversation with your doctor. At what age do these “Seizure Mimics” appear? I will make it very simple to remember: “Benign Neonatal Sleep Myoclonus” is seen only in children less than 6 months of age. All the others start between 6 months to 5 years of age Let us talk about these, one by one. What is Benign Neonatal Sleep Myoclonus? The word “Benign” means harmless. “Neonatal” means in a baby less than 6 months old. “Myoclonus” means jerks. Therefore, the literal translation of this fancy phrase is “harmless jerks of a small baby during sleep”. When babies are less than 6 months old are falling asleep, they may have some jerking of their arms or legs. Surprisingly, this is more common if they sleep immediately after being fed. Isolated jerks while sleeping are often benign. But an EEG is needed to confirm this. Treatment is usually not needed. These episodes end when the baby becomes older. What are “breath-holding spells”? The classical episode of breath-holding happens after an emotional upset – such as being scolded or getting angry. The child cries for a long time and then suddenly holds his/her breath. Their face may turn blue and sweaty, and they lose consciousness. They remain unconscious for about 30 seconds, sometimes up to 1 minute. During this time, the entire body goes limp. When angry, children can hold their breath long enough to pass out! Occasionally the body may become rigid instead, and the arms or legs may jerk. Depending on the severity of this episode, the child may be confused for a few minutes after regaining consciousness. Even though this is not a seizure, it is wise to take the same precautions because the child does lose consciousness. [Click here] Breath-holding spells are primarily a psychological problem. Counselling usually helps the child and medications are generally not required. The episodes typically go away before 5 years of age.  Note: Another variant of “breath-holding” is characterized by the skin becoming pale, instead of blue. These are called pallid-breath-holding spells, or “pallid infantile syncope”. The mechanism of these events is slightly different (a decrease in heart rate caused by intense emotional stimuli). Still, everything else about them – including spontaneously going away by age 5 -is practically the same.  What is “Sandifer Syndrome”? Dr. Paul Sandifer was a famous British neurologist. He noticed that babies who had food reflux sometimes started having strange movements of the neck. One of his Austrian students, Dr. Kinsborne formally documented this observation and named it in his teacher’s honour. Once a baby is fed, and its tummy is full, it tends to be happy. Unfortunately, some babies have a condition in which food does not stay in the stomach. It flows back towards the mouth. This reflux of food and stomach acid is extremely uncomfortable, and the baby may express distress by crying. If he/she is old enough, he/she may point to his stomach or chest as the source of discomfort. Sandifer syndrome is caused by reflux of acid from the stomach to the mouth. For unclear reasons, this problem causes some children to have weird movements of the neck, upper arms and shoulders and sometimes the back as well. The child may arch his/her head backwards, or to turn it to one side. In very severe cases, the child may lie on the floor with and stiffen and arch his/her back intermittently. Babies may express pain by crying and sometimes by strange writhing movements of the body. The episode lasts for a variable time, occasionally up to an hour. The episodes usually stop after antacid and anti-reflux medications. Rarely, there may have a structural problem near the top of the stomach (a hiatal hernia) which may need to be surgically corrected. Can masturbation in children be mistaken for seizures? Even though this topic is seemingly uncomfortable, we need to discuss it here because masturbation is common in children. They do it unknowingly, and  because they are unable to express themselves at their young age, these episodes

At present, we do not have a Miracle Cure for PSP. But that does not mean that a cure will never be available. Diseases such as Hepatitis-C were incurable. They now have cures. We should keep ourselves healthy for the future. Some medications may decrease symptoms. Also, non-medication treatment is essential. Non-medication treatment includes swallowing training and balance training. I am Dr Siddharth Kharkar, a Neurologist in Thane, India and a Neurologist in Mumbai, India. I provide Parkinson’s treatment in India and am an Epilepsy specialist in India. I provide Epilepsy surgery in India at Mumbai & Parkinson’s surgery in India. Let us read about these things. As noted earlier, PSP is different than regular Parkinson’s disease. PSP patients may have all the symptoms of Parkinson’s disease. They also have problems with eye movements (video below) and falling. Click here to know the complete signs. https://www.youtube.com/watch?v=LU7TC0wufhg&t=6s This article is only for patients with PSP. I am Dr Siddharth Kharkar, a Neurologist in Thane, Maharastra, India. I also work as a Neurologist in Mumbai, India. Come, let’s learn together about this important topic. Will a miracle cure for PSP (Progressive Supranuclear Palsy) ever be available? We don’t have such a cure now. But let us put this in perspective. When I was in medical school, medical students were scared of Hepatitis-C. Hepatitis-C is spread like HIV, through nicks and cuts while treating patients. At the time, there was no miracle treatment. If someone were to get it, they developed severe problems like liver failure and liver cancer. Does this disease have a miracle cure now? Yes. In 2013, the US FDA approved a very effective medication. The name of this medication is Sofosbuvir. With other medicines, Sofosbuvir can cure 94-99% of all patients. Sofosbuvir is a near-miraculous cure for some patients with Hepatitis C. It is difficult to predict when such a cure will be available for PSP. Not me, nor any other doctor can make a 100% guaranteed prediction. But, we need to take care of ourselves in the present. We should partake of the available treatment. We need to be ready to bear the future benefits of current research. Levodopa for PSP treatment: As noted in another article, PSP causes decreased dopamine activity in the brain. Levodopa is an oral tablet. It goes into the brain, where it is converted into Dopamine. Levodopa is very useful in Parkinson’s disease. So, people have tried using it in PSP. The benefit of Levodopa in PSP is not predictable. About 25-40% of people benefit. The improvement may be incomplete. Levodopa may also become less effective after some years. Once it enters the brain, Levodopa is converted into Dopamine. Overall, Levodopa can be very helpful, even if it is not a Miracle cure for PSP. But, that is not the complete story. PSP Subtypes and treatment There is increasing awareness that there may be more than one variety of PSP. In 2017, the International Movement Disorders Society (MDS) described 7 variants: PSP-subtype Characteristic 1. PSP-RS (PSP-Richardson) Typical “PSP”, with severe falling and eye movement problems 2. PSP-P (PSP-Parkinsons) Almost identical to Parkinson’s disease 3. PSP-OM (Ocular movement) With eye movement problems 4. PSP-PI (Postural instability) With severe walking problems and falls 5. PSP-CBD, PSP-F, PSP-SL These varieties are rare. It is not essential to remember all these varieties. Please focus on number 2. Number 2 is PSP-Parkinsonism. Which translates into “PSP that behaves like Parkinson’s disease”. PSP-P behaves like Parkinson’s disease in it’s response to Levodopa. Although still partial, Levodopa may have a marked effect on PSP-P. The effect may also last for a longer time, often extending over many years. Some variants of PSP are like Parkinson’s disease. How many people have this variant? That is a matter of great debate. As I mentioned, this research is new, and people are still debating how to classify patients. What it means for you – your response to Levodopa may be better than doctors earlier thought possible. We need to try it. Amantadine for PSP treatment: Amantadine is another medication used in Parkinson’s disease. No one understands how it works. It was initially made to be an Antiviral, against the Flu virus. But doctors found it is useful for Parkinson’s disease. Amantadine can decrease freezing – the feeling that your feet are stuck to the ground. Amantadine may also be useful in PSP. In particular, it may help you in walking better. Patients with PSP may freeze while walking. They feel like they are stuck to the ground. They cant take another step forward. Amantadine may reduce these “freezing” episodes. Most doctors will try Levodopa in PSP. But many do not try Amantadine. Almost all authorities feel it should at least be tried in all patients. The authoritative Marsden’s Textbook of Movement disorders also recommends an Amantadine trial. Other medications for PSP These other medications do not improve movement dramatically. But they can be beneficial for other problems such as depression and trouble opening your eyes. Medication May help with 1. Amitriptyline DepressionMay improve walking. 2. Donepezil Thinking problemsMay decrease “Freezing” 3. CoQ-10 Still in research stagesNot a good option at present May help with movement. 4. Zolpidem Same as above 5. Botox injections An excellent option for a particular problem (see below) Botox injections are often overlooked. In some PSP patients, the muscles around the eye are forcefully contracted all the time. You may not be able to open your eyes. This is called “Blepharospasm”. As you can imagine, not being able to open eyes is a troublesome problem. Botox relaxes muscles. Botox helps to keep the eyes open. Botox is the same medication that some people use to smoothen out skin wrinkles. Here is an excellent video of the process: https://www.youtube.com/watch?v=7BaAanD0lVY&t=60s Botox injections are relatively safe. It takes about 5-10 minutes in the doctor’s office. The main downside is that they are somewhat expensive. Reference / Additional reading: A Review of Treatment Options for Progressive Supranuclear Palsy – Stamelou et al., CNS drugs – 2016 Will Deep Brain Stimulation (DBS) be the Miracle Cure for PSP? DBS is

Certain medications block dopamine activity in the brain. If you don’t have Parkinson’s, they may cause Medication Induced Parkinsonism (also called “drug-induced parkinsonism”). If you have Parkinson’s disease, they can worsen your symptoms. In this condition, Levodopa is not very useful. This is because the sites where levodopa normally attaches are blocked by these nefarious drugs. Therefore, in this condition, both Anticholinergic medications and Amantadine are more effective than levodopa. Let us learn more. Dopamine Blockers First, here are the medications that can block Dopamine activity in the brain. “Joint position” signals going from the ankle joints to the brain are very important for balance. DOPAMINE BLOCKERS: Medications which can produce symptoms like Parkinson’s disease Many medications used for psychiatric problems such as schizophrenia (these are also called “Neuroleptics”) Haloperidol, Risperidal, Olanzapine, Aripiprzole, Trifluoperazine and many more. Clozapine and Quetiapine usually do not cause problems. Some medications for mood and depression Fluphenazine, Tranycypormine, Lithium Some anti-nausea medications Metoclopramide, Levosulpuride, High doses of domperidone about 30-40 mg/day, Flunarazine, rarely cinnarazine Some heart and blood pressure medications Amiodarone, methly-dopa Overall, Neuroleptics (psychiatric) medications are probably the most common cause of Medication Induced Parkinsonism. What is Parkinsonism? Parkinsonism literally means “like Parkinson’s disease”. Certain symptoms usually are seen in Parkinson’s disease. If a person has these symptoms, he is said to have Parkinsonism. Parkinson’s disease is the most common cause of Parkinsonism. The second most common cause in many countries is Medication Induced Parkinsonism. What is Dopamine Blockade? Dopamine is a chemical in our brains. It helps us to move. Medication Induced Parkinsonism is caused by medications which block the action of dopamine. These nefarious medications do this by blocking the microscopic sites in the brain where dopamine usually attaches itself. There is no death of cells. Dopamine-blocking medications block the sites in Brain cells where Dopamine normally attaches. Now, dopamine cannot attach itself anywhere! It stops having any effect! The cells do not die. On the other hand, in typical Parkinson’s disease, there is the actual death of cells in the Substantia Nigra (Click Here). Therefore, these processes are very different from one another. In addition, the symptoms produced by “Medication Induced Parkinsonism” are also somewhat distinct. There is usually no tremor and both sides are equally affected. Medication Induced Parkinsonism can progress very rapidly, whereas Parkinson’s disease usually progresses very slowly. Why is levodopa not useful in Medication-Induced Parkinsonism? Levodopa gets converted into dopamine in the brain. But then it has nowhere to attach! Once it enters the brain, Levdoopa is converted into Dopamine. Therefore, levodopa is not very useful in medication-induced Parkinsonism. Anti-cholinergic medications Dopamine has an enemy in the brain, called Acetylcholine. Acetylcholine actually is a good chemical with a lot of beneficial effects, but one of the things it does is to reverse some of the actions of Dopamine. Trihexyphenidyl (Pacitane) and Benztropine are the most commonly used Anticholinergic Medications. By decreasing the effect of acetylcholine (dopamine’s enemy), these medications give Dopamine a free hand in the brain. Anti-cholinergic medications: Side effects I (and many other doctors) believe that Trihexyphenidyl (Pacitane) and related medications should not be used in the elderly, at least not routinely. Acetylcholine is a very important chemical in the body, and blocking it can produce many unwanted side-effects. Therefore the most common, and frequently serious side-effects with the use of these medications are: Confusion – The patient may lose track of day and night. He/She gets confused easily, has trouble paying attention or remembering anything. In very severe cases, the patient can have visual hallucinations and become physically violent! Anticholinergics can cause confusion. Acute urinary retention – This happens more frequently in males. The urinary bladder fills up with urine, but because of the anticholinergics, the path for urine to get out is closed! The patient starts becoming very, very uncomfortable because of the ever-increasing size of the bladder, which causes severe abdominal pain. This sometimes requires the urgent insertion of a catheter. Glaucoma – Similar to what happens with urine, these medications can cause shut off the flow of fluid away from the eye. They make the pupil very large, blocking all the drainage pipes in the periphery of the eye. As a result, fluid keeps accumulating within the eye, and it starts becoming larger. The eye is not a very flexible, and therefore the pressure inside it increases rapidly, and this can cause severe eye pain and blindness. Immediate medical treatment is needed! Sometimes, anticholinergics can cause “Glaucoma” – which is an uncontrolled increase in pressure inside the eye. Amantadine Is Amantadine a better treatment for medication-induced Parkinsonism? Yes, I think so. I think so because it is equally effective and the side-effects of amantadine are relatively modest. In patients without kidney disease, Amantadine usually does not have any side-effects other than some minor leg swelling and redness. Amantadine was originally made to treat viral colds. Incidentally, doctors found it to be a stellar medication for Parkinson’s disease, including medication-induced Parkinsonism. One has to be careful while using it in patients with renal failure. Amantadine is excreted by the kidneys and therefore it accumulates in the body if you have renal failure. If it accumulates up to a toxic level, you may become confused and have jerking of the body (myoclonus). Future Does the development of “Medication Induced Parkinsonism” predict the development of “Parkinson’s disease” later in life? No, not in the majority of cases. However, some patients have a dopamine deficiency and are on the brink of developing symptoms due to Parkinson’s disease. If a person is on the brink of developing symptoms, dopamine-blocking medications lead to appearance/worsening of Parkinsonian symptoms. In these patients, dopaminergic blocking medications may cause sudden appearance/worsening of these symptoms. Physical therapy, especially balance training, can help to delay onset of Parkinson’s disease. So, in some (but not all) cases, the development of medication-induced parkinsonism may indicate that the patient may develop Parkinson’s disease later in life. Caution: This information is not a substitute for professional care. Do not change your medications/treatment without your doctor’s permission.

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Parkinson’s and falling, unfortunately, go hand in hand. Most patients with Parkinson’s disease have some imbalance. In uncomplicated Parkinson’s disease, falls are less common. But: If you have recurrent falls or If you are falling backwards, Parkinson’s disease may not be the right diagnosis. If you do have Parkinson’s disease, adequate treatment helps you move properly. This prevents falls. In addition, a few general measures may also help to prevent falls and avoid serious injuries. Let us learn more. How do we maintain our balance? When the joints in your legs move, the nerves in your legs send signals to the spinal cord, from where they go to the Brain. If this system is working, then the Brain knows *exactly* where your legs are, even when your eyes are closed! This ability is called “Joint Position Sense”. “Joint position” signals going from the ankle joints to the brain are very important for balance. There are many nerves in the arms and legs (blue). These send joint position signals to the spinal cord (red), which in turn sends them to the brain (pink). A problem anywhere in this pathway can cause problems in maintaining balance. A second device is important as well: Our inner ears contain tiny circular canals filled with fluid. When your head moves, the liquid inside these canals moves, and the ears immediately send signals to the brain, informing it of this movement. The internal ear has delicate canals filled with fluid which detect head movement. Finally, your eyes. This one is obvious. When you tend to fall, you can see that you are falling. The eyes almost instantaneously send this information to the Brain, so that corrective action can be taken. Our eyes send signals to our brain almost instantaneously. The Brain is supposed to act immediately when it gets signals from any of these organs (joints/ears/eyes) that you are going to fall down. These reflex movements are called “Postural reflexes”. With this understanding, let us see now why we fall. Why do patients with Parkinson’s disease fall? In simple terms, patients with Parkinson’s disease fall down because of 3 reasons: Poor input, Poor postural reflexes, Freezing. 1. Poor input: This problem is often overlooked. When thinking about Parkinson’s and falling, we need to remember that Parkinson’s patients can also have other diseases. Let us say you have a problem with your eyes. Everything is blurred. Now, you start to walk. But…. your brain is not getting any input. It does not know where your limbs are! So, you become unsteady! Proper eyeglasses enable you to see clearly and reduce falls. So: Problems in your joints, muscles or leg nerves – e.g. Diabetes, Vitamin D deficiency Problems in your spinal cord – e.g. compression, vitamin B12 deficiency Problems in your ears – e.g. infections Problems in your eyes – e.g. improper glasses, cataracts Increase the risk of falling tremendously. This is true even if you do not have Parkinson’s disease! But let us look at 2 reasons specific to Parkinson’s disease: 2. Poor postural reflexes:1. Poor input: Let us say your brain is getting all the inputs it needs. It now knows where your limbs are. But in Parkinson’s disease, the brain becomes slow. For unclear reasons, it does not respond to these inputs immediately. This problem is called “Poor Postural Reflexes”. Poor postural reflexes: The brain is slow in processing inputs and outputs needed for balancing. Let’s imagine you catch your foot in the carpet. When you start to fall, your brain is too slow to take corrective measures. It does nothing. So you fall. This is one of the reasons for Parkinson’s and falling. 3. Freezing: When walking, you may sometimes feel like you are stuck to the ground. This is called “Freezing”. If this happens suddenly, your upper body may continue moving and you may fall forwards. If your movement problems are incompletely treated, you can “Freeze” suddenly while walking and fall forwards. Is freezing really the reason for falling? Some people believe that “freezing” while walking can lead to falls. In contrast, other people believe that the freezing before falling is an erroneous reflex by the Brain, which is just trying to prevent a process of falling which has already started happening. Regardless of what comes first, it is clear that making movements more rapid with proper treatment helps to prevent falls. So, how can you prevent falls? The first step is to identify why you are falling. The relative contribution of these factors to falling is different in different patients. Thoughtful collaboration with your neurologist should help to identify your most critical problems. We will look at each of these things in detail, one by one. If you have Parkinson’s and falling backwards, a very important possibility arises. Your doctor should carefully examine you for signs of PSP. PSP is described in another article [Click here]. Careful examination & collaboration usually identifies 1-3 critical problems causing falls. Prevent a drop in Blood Pressure on standing When you get up suddenly from a chair or bed, your blood rushes into your legs. This causes blood pressure to drop. You may become light-headed & fall. This is called Orthostatic Hypotension. It is very common in Parkinson’s disease. You can read more in another article, but here is a quick summary: Prevent Orthostatic Hypotension 1. Avoid medications that may worsen this problem. 2. Drink enough water. 3. If your doctor agrees, slightly increase salt in your diet. 4. Stand up gradually. 5. Exercise & develop better muscle tone. 6. Ask your doctor for medications. Adequate sensory input A neurological examination can test the input organs (nerves, spinal cord, ear, eyes). For example, your may ask you to close your eyes and move your big toe up and down. If you are unable to tell whether it is up or down, it indicates there is something wrong with your “joint position sense”. Your neurologist may ask you do some tests: Tests to check sensory organs (input) 1. Nerve conduction studies 2. MRI of the spine 3. Blood tests – Vitamin B12, Folic acid, E & Copper, Syphilis &