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Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) What is the Parkinson's Disease? Parkinson’s disease is a brain disorder that leads to shaking , stiffness , and difficulty with walking, balance, and coordination . Parkinson’s symptoms usually begin gradually  and get worse over time. As the disease progresses, people may have difficulty walking  and talking . They may also experience mental and behavioural changes , sleep problems , depression , memory difficulties , and fatigue . Both men and women can have Parkinson’s disease. However, the disease affects about 50 percent more men than women . One clear risk factor for Parkinson’s is age . Although most people develop the disease around age 60 , about 5 to 10 percent  of people have early-onset Parkinson’s , which begins before age 50 . Early-onset forms are often, but not always, inherited and may be linked to specific gene mutations . What causes Parkinson’s disease? Parkinson’s disease occurs when nerve cells (neurons)  in the area of the brain that controls movement become impaired or die . Normally, these neurons produce dopamine , a critical brain chemical. When they are lost or impaired, dopamine levels drop, causing the movement problems  associated with Parkinson’s. People with Parkinson’s also lose nerve endings that produce norepinephrine , which controls many automatic body functions  like heart rate and blood pressure. The loss of norepinephrine may explain non-movement symptoms , such as: Fatigue Irregular blood pressure Slow digestion Sudden blood pressure drops when standing up Many brain cells of people with Parkinson’s contain Lewy bodies —unusual clumps of the protein alpha-synuclein . Scientists are studying how this protein and certain genetic mutations  relate to Parkinson’s and Lewy body dementia . While some cases are hereditary or linked to genetic mutations , most cases occur randomly  and do not run in families. Many researchers believe Parkinson’s results from a combination of genetic and environmental factors , including toxin exposure . Symptoms of Parkinson’s disease Parkinson’s disease has four main symptoms: Tremor  (in hands, arms, legs, jaw, or head) Stiffness  of the limbs and trunk Slowness of movement Impaired balance and coordination , sometimes leading to falls Other symptoms may include: Depression and emotional changes Difficulty swallowing, chewing, and speaking Urinary problems or constipation Skin problems Sleep disruptions Symptoms and progression vary among individuals. Early symptoms can be subtle  and are often dismissed as normal ageing . There are no definitive medical tests for Parkinson’s, making diagnosis challenging. Early signs may include: Mild tremors Difficulty rising from a chair Soft speech Small, cramped handwriting Loss of facial expression or arm swing Parkinsonian gait: leaning forward, small steps, reduced arm swing Trouble initiating or continuing movement Symptoms typically begin on one side  of the body, eventually affecting both—though often more severely on the original side. Many people also report early non-motor symptoms , such as: Sleep problems Constipation Reduced sense of smell Restless legs Diagnosis of Parkinson’s disease Advanced neuroimaging with PET of the brain Many disorders mimic Parkinson’s symptoms. When caused by other factors, these are termed parkinsonism. Some may initially be misdiagnosed, but specific tests and responses to medication help distinguish them. There are currently no blood or lab tests  to diagnose non-genetic Parkinson’s. Diagnosis is based on: Medical history Neurological examination Improvement with medication , a key hallmark of Parkinson’s Treatment of Parkinson’s disease While there is no cure , treatment can relieve symptoms  through medications , surgery , and therapies . Medicines for Parkinson’s disease Medications may: Increase dopamine levels Affect other brain chemicals Control non-motor symptoms Main therapy involves dopamine-replacement drugs , usually taken with medications to reduce side effects  (nausea, vomiting, low blood pressure, restlessness). Warning:  Patients should never stop medication  without consulting their doctor. Abruptly stopping can cause serious complications , such as immobility  or breathing difficulties . Other medications include: Dopamine agonists  – mimic dopamine MAO-B inhibitors  – slow dopamine breakdown COMT inhibitors  – help dopamine persist Amantadine  – an old antiviral that reduces involuntary movements Anticholinergics  – reduce tremors and rigidity Deep brain stimulation (DBS) For patients not responding well to medication, DBS  may be appropriate. This involves: Implanting electrodes  into the brain Connecting them to a small device  implanted in the chest Painlessly stimulating the brain  to relieve tremor , slowness , and rigidity DBS is an established treatment  for advanced Parkinson’s.— Dr Prem Pillay , Singapore neurosurgeon trained at the Cleveland Clinic-USA , now Medical Director at Singapore Brain Spine Nerves Center Other therapies Supportive therapies include: Physical, occupational, and speech therapy Neuropsychological assessment and support Aquatic physiotherapy Table tennis for Parkinson’s disease  – helps with muscle coordination and balance Healthy diet and quality sleep Conclusion Parkinson’s disease is a complex condition, but with early diagnosis and tailored treatments, individuals can continue to lead fulfilling lives. If you or your loved one are experiencing symptoms such as tremors or changes in movement, consult a healthcare professional promptly. For expert care and support, contact the Singapore Brain Spine Nerves Center today. References and acknowledgements National Institutes of Health – USA Singapore Brain Spine Nerves Center Table Tennis for Good Foundation

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) What is Trigeminal Neuralgias? The 5th cranial nerve also known as the trigeminal nerve is the nerve that supplies feeling and movement to the face. Trigeminal neuralgia is a troublesome pain in the face that may be caused by a tumor pressing on the trigeminal nerve or a blood vessel that presses on the trigeminal nerve. In some patients the cause cannot be determined. In 5% of patients, trigeminal neuralgia may be associated with multiple sclerosis. How is Trigeminal Neuralgia Diagnosed? Trigeminal Neuralgia is diagnosed by the clinical symptoms of pain in the face that is quite disturbing and can be triggered by hot or cold food/drinks, brushing the teeth, air blowing on the face or touching the face. The pain can have a nerve irritation quality which includes being tingly, burning, electric zapping in nature and sometimes so severe that people have to stop their activities and sit still or lie down. It may involve the forehead, cheek or chin area. It can come and go randomly. Dr Prem Pillay usually does an MRI of the Brain to make sure there is no tumor such as a meningioma or acoustic neuroma pressing the trigeminal nerve and causing face pain. Blood vessels touching the Trigeminal Nerve can also be visualised on MRI. Treatment of trigeminal neuralgia Stereotactic radiosurgery Gamma Knife A no open surgery  method that is non-invasive, effective, precise , and lower risk  than surgery. It is a day treatment  for most patients. Other minimally invasive procedures Radiofrequency electrocoagulation Glycerol injection Balloon compression of the Gasserian ganglion Microvascular decompression (MVD) A surgery  where an opening is made in the skull behind the ear , and microsurgery  is done to find the root cause of trigeminal nerve compression .This is usually a blood vessel , which is then elevated off the nerve  and kept there using a Teflon patch . Stereotactic surgery / Gamma Knife for trigeminal neuralgia Stereotactic radiosurgical treatment  of trigeminal neuralgia is the most recent  and least invasive  neurosurgical option.It is the treatment least likely to cause complications , as no surgical opening  is made, avoiding the major risks of surgery such as: Infection Bleeding Death Also, the risk of facial numbness  and new facial sensations (dysesthesias)  is much lower  than with other surgical procedures. Suitable candidate Any patient with trigeminal neuralgia who has: Failed medical therapies  (due to lack of pain relief or undesirable side effects) Older patients  or those with other medical conditions Previously undergone failed surgical procedures … is an excellent candidate  for stereotactic radiosurgery / Gamma Knife . Gamma Knife or LINAC radiosurgery? Both the Linear Accelerator (LINAC)  and the Gamma Knife  are used in stereotactic radiosurgery . The Gamma Knife  is a highly precise system  with good results in the hands of experienced neurosurgeons . It is a day treatment . How does stereotactic radiosurgery / Gamma Knife work to treat trigeminal neuralgia? Stereotactic radiosurgery / Gamma Knife delivers a high dose of gamma rays in one session  to the target lesion  with scalpel-like precision , causing minimal damage to surrounding tissue . The target  is the trigeminal nerve  near where it exits the brain. A stereotactic frame or navigation box  is fixed to the patient’s head. It is a day-surgery procedure . The patient can return to normal activities  immediately after treatment. 4 stages of stereotactic radiosurgery treatment Stage 1 A navigation box  is firmly fixed to the patient’s head.This allows for precision and accuracy  during treatment. Stage 2 The patient undergoes a treatment planning MRI  of the brain. Stage 3 The neurosurgeon and team  (radiation oncologist and physicist) use 3D computer imaging  to: Plan the treatment Determine the radiation dose The neurosurgeon  is the leader of the team , as he is the brain expert . Stage 4 The patient lies down on the treatment couch for the radiosurgery session , which is: Painless Non-invasive After treatment, the navigation box is removed , and the patient usually goes home the same day . What are the results? Studies done in Sweden, the USA, Japan and Singapore show that good pain relief is obtained in the majority of people with Trigeminal Neuralgia. Conclusion Trigeminal Neuralgia is a debilitating condition that requires a tailored approach for effective management. Early diagnosis and treatment can make a significant difference in reducing pain and restoring quality of life. If you or someone you know is experiencing symptoms of trigeminal neuralgia, consult the specialists at Singapore Brain Spine Nerves Center for compassionate and comprehensive care. Let us guide you on your journey to pain relief and improved well-being.

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) Your headache symptoms can help your doctor determine its cause and the appropriate treatment. Most headaches aren’t the result of a serious illness, but some may result from a life-threatening condition requiring emergency care. Headaches are generally classified by cause: Primary headaches: A primary headache is caused by overactivity of or problems with pain-sensitive structures in your head. A primary headache isn’t a symptom of an underlying disease. Chemical activity in your brain, the nerves or blood vessels surrounding your skull, or the muscles of your head and neck (or some combination of these factors) can play a role in primary headaches. Some people may also carry genes that make them more likely to develop such headaches. The most common primary headaches are: Cluster headache Migraine Migraine with aura Tension headache Trigeminal autonomic cephalalgia (TAC), such as cluster headache and paroxysmal hemicrania A few headache patterns also are generally considered types of primary headache, but are less common. These headaches have distinct features, such as an unusual duration or pain associated with a certain activity. Although generally considered primary, each could be a symptom of an underlying disease. They include: Chronic daily headaches (for example, chronic migraine, chronic tension-type headache, or hemicranias continua) Cough headaches Exercise headaches Sex headaches Some primary headaches can be triggered by lifestyle factors, including: Alcohol, particularly red wine Certain foods, such as processed meats that contain nitrates Changes in sleep or lack of sleep Poor posture Skipped meals Stress Secondary headaches A secondary headache is a symptom of a disease that can activate the pain-sensitive nerves of the head. Any number of conditions — varying greatly in severity — may cause secondary headaches. Possible causes of secondary headaches include: Acute sinusitis (sinus infection) Arterial tears (carotid or vertebral dissections) Blood clot (venous thrombosis) within the brain — separate from stroke Brain aneurysm (a bulge in an artery in your brain) Brain AVM (arteriovenous malformation) — an abnormal formation of brain blood vessels Brain tumor Carbon monoxide poisoning Chiari malformation (structural problem at the base of your skull) Concussion Dehydration Dental problems Ear infection (middle ear) Encephalitis (brain inflammation) Giant cell arteritis (inflammation of the lining of the arteries) Glaucoma (acute angle closure glaucoma) Hangovers High blood pressure (hypertension) Influenza (flu) and other febrile (fever) illnesses Intracranial hematoma Medications to treat other disorders Meningitis Monosodium glutamate (MSG) Overuse of pain medication Panic attacks and panic disorder Post-concussion syndrome Pressure from tight headgear, such as a helmet or goggles Pseudotumor cerebri Stroke Toxoplasmosis Trigeminal neuralgia (as well as other neuralgias, all involving irritation of certain nerves connecting the face and brain) Some types of secondary headaches include: External compression headaches (a result of pressure-causing headgear) Ice cream headaches (commonly called brain freeze) Medication overuse headaches (caused by overuse of pain medication) Sinus headaches (caused by inflammation and congestion in sinus cavities) Spinal headaches (caused by low pressure or volume of cerebrospinal fluid, possibly the result of spontaneous cerebrospinal fluid leak, spinal tap or spinal anesthesia) Thunderclap headaches (a group of disorders that involves sudden, severe headaches with multiple causes) Dr Prem Pillay, an Expert on Headaches recommends that if they are severe and /or persistent that you have a consult which may include a Neurological examination and imaging including MRI of the Brain. Serious problems such as Brain Tumor or a ruptured Brain Aneurysm or Arterio Venous Malformation are not common but if not detected early have serious life changing consequences. Conclusion Headaches are a common yet diverse condition that can significantly impact the quality of life. Understanding the type and cause of headaches is essential for effective management. At Singapore Brain Spine Nerves Center, our team offers expert evaluation and tailored treatment plans for all types of headaches. If you or a loved one are struggling with recurring or severe headaches, seek professional medical advice to improve your comfort and well-being. Visit the Singapore Brain Spine Nerves Center today to learn more.

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) What Are Cerebral Cavernous Malformations? Cerebral cavernous malformations (CCMs) , also known as cavernous hemangiomas , cavernous angiomas , or cavernomas , are abnormal clusters of blood vessels  in the brain or spinal cord [1][3]. Dr Prem Pillay  explains that these lesions are characterised by their distinctive appearance , resembling small mulberries , and are composed of closely packed, thin-walled blood vessels  [5]. CCMs contain slow-moving or clotted blood  and lack the normal junctions with surrounding cells, leading to potential leakage into adjacent tissues  [1]. Unlike tumours, CCMs do not exhibit endothelial hyperplasia  and are considered vascular malformations rather than neoplasms  [1]. These lesions can vary in size but are typically less than 1 centimetre in diameter  [5].They can be found in various locations within the central nervous system, including the white matter of the brain , the cerebral cortex , and the spinal cord  [1] Causes and Genetic Factors The aetiology of CCMs  is complex and can be attributed to both sporadic occurrences  and genetic factors . In many cases, CCMs develop sporadically as single lesions  without a clear hereditary component [5]. However, a significant proportion of cases are associated with specific genetic mutations . Genetic Basis of Cavernomas / CCMs CCMs can be inherited in an autosomal dominant  pattern, caused by mutations in three primary genes: CCM1 (KRIT1) CCM2 (MGC4607 or malcavernin) CCM3 (PDCD10)  [1] These genes play crucial roles in maintaining the integrity of blood vessels .Mutations leading to loss of function  in these genes are believed to be responsible for the formation of CCMs [1]. The “second hit mutation” theory  suggests that a combination of inherited and acquired mutations  may contribute to the development of multiple lesions  in some patients [1]. Diagnosis of CCMs / Cavernomas Accurate diagnosis of CCMs is essential for proper management and treatment planning . Common diagnostic methods include: Magnetic Resonance Imaging (MRI) MRI is the gold standard  for diagnosing CCMs. On T2-weighted images , CCMs typically appear as high-signal lesions  [1]. Gradient-echo  or susceptibility-weighted sequences  can enhance the detection of small or multiple lesions. Computed Tomography (CT) CT may show CCMs as areas of increased density , often with calcifications . MRI is preferred due to superior soft tissue contrast  and ability to detect smaller lesions  [1]. Angiography CCMs are angiographically occult  and do not appear on conventional angiograms [3]. Cerebral angiograms  are useful to distinguish CCMs from small arteriovenous malformations (AVMs)  or concurrent AVMs/AV fistulas . Genetic Testing For patients with a family history  or multiple lesions , genetic testing for CCM1, CCM2, and CCM3  can confirm diagnosis and guide management [3]. Treatment Options The management of CCMs is tailored to each patient’s presentation , lesion location , and symptoms .As a Cavernoma expert , Dr Prem Pillay  offers a comprehensive treatment approach using the latest advancements  in neurosurgery  and radiosurgery . Conservative Management For asymptomatic lesions  or those in deep, eloquent brain areas , a watchful waiting approach  may be appropriate.This includes: Regular MRI monitoring  to track growth or changes [6] Lifestyle modification guidance  and identifying potential triggers  to reduce risk Microsurgical Resection Surgical removal is the definitive treatment  for symptomatic CCMs, particularly those causing recurrent haemorrhages  or intractable seizures  [8]. Dr Prem Pillay  employs state-of-the-art techniques to maximise safety and efficacy: Frameless stereotaxy  for precise lesion localisation Intraoperative functional MRI  to map critical brain areas Computer image-guided surgical navigation  for optimal planning [7] The goal is complete resection  while preserving healthy tissue — shown to provide excellent outcomes in epilepsy control  and haemorrhage prevention  [8]. Stereotactic Radiosurgery (SRS) For deep-seated lesions  in eloquent areas or for patients unfit for surgery , SRS is a valuable alternative [8]. Uses highly focused radiation beams  to target CCMs precisely Reduces risk of future haemorrhages Performed with Gamma Knife  or LINAC Radiosurgery  using robotic assistance Day procedure : scarless, painless, and involves no cutting Medical Management While there is no medication to treat CCMs directly , symptom management includes: Anticonvulsants  for seizure control Pain management  for headaches Steroids  to reduce perilesional oedema when indicated [4] Ongoing Research and Future Directions As a Neurosurgeon with CCM expertise , Dr Prem Pillay  actively follows cutting-edge research to improve outcomes. Current focus areas include: Novel pharmacological agents  targeting CCM signalling pathways Advanced imaging techniques  for better lesion characterisation Minimally invasive surgical approaches  for deep lesions Conclusions Cerebral cavernous malformations  are complex vascular lesions that require expert management .With many years of experience and access to advanced technology , Dr Prem Pillay  delivers the highest standard of care  — from accurate diagnosis to tailored treatments. If you or a loved one has been diagnosed with a CCM , we encourage you to consult with our specialised team .Together, we can create a comprehensive treatment strategy  tailored to your unique needs and goals. Citations [1] https://en.wikipedia.org/wiki/Cavernous_hemangioma [2] https://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/cavernous-malformations [3] https://www.ninds.nih.gov/health-information/disorders/cerebral-cavernous-malformations [4] https://www.healthline.com/health/cavernous-hemangioma [5] https://www.mayoclinic.org/diseases-conditions/cavernous-malformations/symptoms-causes/syc-20360941 [6] https://my.clevelandclinic.org/health/diseases/21594-cavernous-hemangioma [7] https://www.mountsinai.org/locations/cerebrovascular-center/conditions/vascular-malformations/cavernomas [8] https://pmc.ncbi.nlm.nih.gov/articles/PMC4300037/ [9] https://www.mayoclinic.org/diseases-conditions/cavernous-malformations/diagnosis-treatment/drc-20360942

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) Spot a Stroke: BE FAST Stroke  remains a leading cause of death and long-term disability worldwide, including Singapore and Asia, affecting over 10 million people annually  [4]. However, recent breakthroughs in diagnosis, treatment, and rehabilitation  offer new hope for patients and their families. This summary provides an overview of the latest advances in stroke care , emphasising the critical importance of rapid intervention  and highlighting promising new approaches  to improve outcomes. Understanding Stroke A stroke  occurs when there is a disruption of blood flow to the brain , either due to a blockage (ischaemic stroke)  or a rupture of a blood vessel (haemorrhagic stroke)  [4]. This interruption deprives brain cells of oxygen, causing damage and potential cell death. The effects of a stroke can vary widely depending on the location and extent of the brain injury . Ischaemic stroke  needs to be quickly identified and treated with anti-platelet and anti-coagulant therapy  and endovascular therapy . Patients with TIAs  and RINDs  should be effectively screened with MRA  and DSA  for treatable carotid artery stenosis . Patients with haemorrhage from brain AVMs, aneurysms, cavernomas, and dural AV fistulas  should be diagnosed early with CT, MRI, and DSA . Some patients require early surgery including microsurgery . Selected patients will benefit from endovascular therapy  including embolisation, coiling, flow diverters , and others from stereotactic radiosurgery . The Urgency of Stroke Treatment One of the most critical factors in stroke treatment is time . The phrase “time is brain”  underscores the importance of rapid intervention to limit cerebral damage [1]. Recent research has reinforced the need for urgent action, even when symptoms appear to resolve quickly. Transient Ischaemic Attacks (TIAs) New guidelines emphasise that even brief stroke symptoms , lasting less than an hour (known as transient ischaemic attacks  or TIAs ), require immediate medical attention  [7]. These “warning strokes” can precede a full-blown stroke and should be treated as medical emergencies . Advances in Stroke Diagnosis Early and accurate diagnosis is crucial for effective stroke treatment. Recent technological advancements have improved our ability to quickly identify and characterise strokes. Portable MRI Technology Researchers have developed a portable MRI machine  that can be brought to a patient’s bedside, potentially reducing delays in diagnosis [4]. This innovation allows for faster imaging and could significantly improve the speed of stroke diagnosis and treatment initiation. Cutting-Edge Stroke Treatments The landscape of stroke treatment has evolved rapidly in recent years, with several groundbreaking approaches  showing promise. Endovascular Interventions Mechanical thrombectomy , a procedure to remove blood clots from large vessels in the brain, has emerged as a highly effective treatment  for certain types of ischaemic strokes [5]. Bleeding from AVMs  can be treated with endovascular embolisation . Aneurysms  can be occluded with platinum coils  or excluded from circulation with flow diverters . Subdural haematomas  can be treated using endovascular embolisation  of the middle meningeal artery . Thrombolysis Intravenous thrombolysis  with recombinant tissue plasminogen activator (rt-PA)  remains a cornerstone  of acute ischaemic stroke treatment [1].Recent studies have explored: Extending the time window  for treatment Alternative thrombolytic agents  like tenecteplase  [8] Brain Stimulation Techniques Non-invasive brain stimulation , such as: Repetitive transcranial magnetic stimulation (rTMS) Transcranial direct current stimulation (tDCS) …are being studied for their potential to enhance motor recovery  after stroke [6]. Neuroprotective Strategies Research is ongoing into neuroprotective therapies  that could be administered early — potentially even before imaging  — to limit brain damage in stroke patients [1]. Rehabilitation and Recovery Stroke rehabilitation has seen significant advancements, with new technologies and approaches offering hope for improved recovery. Brain-Computer Interfaces (BCIs) BCIs  are emerging as a promising tool for rehabilitation, allowing patients to control external devices  using brain signals  [10]. This may help stimulate neuroplasticity  and improve motor function recovery . Virtual Reality and Robotics Virtual reality  and robot-assisted therapies  are being integrated into rehabilitation programmes, offering new ways to engage patients and provide intensive, targeted therapy  [6][10]. Personalised Rehabilitation There is a growing emphasis on tailoring rehabilitation strategies to individual patients , considering: Stroke type Stroke location Patient’s specific deficits and goals [3] Prevention and Secondary Stroke Risk Reduction Blood Pressure Management Recent research highlights the importance of personalised blood pressure management  in the acute phase after a stroke [4]. Optimal targets may vary by patient. Antiplatelet Therapy Dual antiplatelet therapy  (aspirin + clopidogrel) has shown promise in preventing recurrent strokes  in certain high-risk patients [8]. Lifestyle Modifications Encouraging: Healthy diet Regular exercise Smoking cessation …remains a cornerstone  of stroke prevention. Future Directions in Stroke Care The field of stroke care is rapidly evolving, with several exciting areas of research underway: Cell therapies Stem cell treatments for stroke recovery show potential for improving motor function  [10]. Artificial intelligence AI is being explored to enhance diagnosis, treatment selection, and outcome prediction . Telemedicine and telerehabilitation Expanding access to specialised care , especially in underserved regions  [6]. Combination therapies Integrating techniques like brain stimulation  with robotic rehab  and traditional therapy [6]. The landscape of stroke care is rapidly evolving, with new technologies  and treatment approaches  offering hope for improved outcomes. From faster diagnosis  and more effective acute interventions  to innovative rehabilitation techniques , these advancements are transforming the way we approach stroke care. However, the most critical factor  remains rapid recognition and response to symptoms . Public education  about warning signs and the importance of immediate medical attention  is crucial. Remember: If you or someone you know experiences symptoms of a stroke , even if they seem to resolve quickly, seek emergency medical care immediately . Every minute counts  in preserving brain function and improving recovery. Stroke Care with Singapore Brain Spine Center With many years of experience in diagnosing strokes and access to the latest technological advancements, Dr Prem Pillay  offers patients the highest standard of care . From accurate diagnosis  to tailored treatment plans , our approach ensures the best possible outcomes  for individuals affected by this challenging condition. If you or a loved one has been diagnosed with a stroke, we welcome you to seek consultation with our specialised team. Together, we can develop a comprehensive, evidence-based, and personalised treatment strategy  that addresses your unique needs and aims to provide the best chance for a positive outcome . References [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC1448697/ [2] https://www.mayoclinic.org/diseases-conditions/stroke/diagnosis-treatment/drc-20350119 [3] https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1402729/full [4] https://www.yalemedicine.org/news/3-stroke-breakthroughs [5] https://bmjmedicine.bmj.com/content/2/1/e000407 [6] https://pmc.ncbi.nlm.nih.gov/articles/PMC10650295/ [7] https://www.stroke.org/en/news/2023/01/19/stroke-symptoms-require-emergency-treatment-even-if-they-quickly-disappear-new-report-says [8] https://pmc.ncbi.nlm.nih.gov/articles/PMC8407466/ [9] https://www.ihi.europa.eu/news-events/newsroom/umbrella-project-sets-sights-stroke-care-revolution [10] https://pmc.ncbi.nlm.nih.gov/articles/PMC10761524/

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) Epilepsy is a disorder of the brain characterised by repeated seizures. A seizure  is usually defined as a sudden alteration of behaviour due to a temporary change in the electrical functioning of the brain. Normally, the brain continuously generates tiny electrical impulses in an orderly pattern. These impulses travel along neurons, the network of nerve cells in the brain and throughout the whole body via chemical messengers called neurotransmitters. In epilepsy, the brain’s electrical rhythms have a tendency to become imbalanced, resulting in recurrent seizures. In patients with seizures, the normal electrical pattern is disrupted by sudden and synchronised bursts of electrical energy that may briefly affect their consciousness, movements or sensations. Epilepsy  is usually diagnosed after a person has had at least two seizures  that were not caused by some known medical condition, such as alcohol withdrawal or extremely low blood sugar. If seizures arise from a specific area of the brain, then the initial symptoms of the seizure often reflect the functions of that area. The right half of the brain controls the left side  of the body, and the left half controls the right side . For example, if a seizure starts from the right side of the brain in the area that controls movement in the thumb, then the seizure may begin with jerking of the left thumb or hand. Types of Seizures Seizures vary so much that epilepsy specialists frequently reclassify seizure types. Typically, seizures belong in one of two basic categories: Primary generalised seizures Begin with a widespread electrical discharge involving both sides of the brain at once. Partial seizures Begin with an electrical discharge in one limited area of the brain. Epilepsy  in which the seizures begin from both sides of the brain at the same time is called primary generalised epilepsy . Hereditary factors  are important in primary generalised epilepsy, which is more likely to involve genetic factors than partial epilepsy  — a condition in which the seizures arise from a limited area of the brain. Some partial seizures  are related to head injury, brain infection, stroke or tumour , but in most cases, the cause is unknown. One question that is used to further classify partial seizures is whether consciousness  (the ability to respond and remember) is impaired or preserved. Factors That May Increase Seizure Risk Stress Sleep deprivation or fatigue Insufficient food intake Alcohol use or drug abuse Failure to take prescribed anticonvulsant medical therapy About half of the people  who have one seizure without a clear cause will have another one, usually within six months. A person is twice as likely  to have another seizure if there is a known brain injury or other type of brain abnormality. If the patient has two seizures, there is about an 80 percent chance  of having more. If the first seizure occurred at the time of an injury or infection in the brain, it is more likely the patient will develop epilepsy than if the seizure did not happen at the time of injury or infection. Prevalence and Incidence According to the Epilepsy Foundation , epilepsy affects three million people in the U.S.  and 50 million worldwide . Seizures may be tied to a brain injury or genetics , but for 70 percent of patients , the cause is unknown. 10 percent  of people will have seizures in their lifetime. More than 300,000 children  under the age of 15 have epilepsy, with 90,000  of them having seizures that cannot be adequately treated. The onset rate increases with age, particularly in cases of stroke, brain tumours, or Alzheimer’s disease . Over 570,000 adults  over 65 suffer from the disorder. More men  than women have epilepsy. Children and adolescents  are more likely to have epilepsy of unknown or genetic origin. Brain injury or infection  can cause epilepsy at any age. The Epilepsy Foundation reports: 70 percent  of children and adults with newly diagnosed epilepsy can enter remission after five years without a seizure while on medication. 75 percent  of people who are seizure-free on medication can eventually be weaned off it. 20 percent  of patients have intractable seizures  — seizures that do not respond to treatment. Epilepsy Risk Factors Premature birth or low birth weight Trauma during birth (such as lack of oxygen) Seizures in the first month of life Abnormal brain structures at birth Bleeding into the brain Abnormal blood vessels in the brain Serious brain injury or lack of oxygen to the brain Brain tumours Infections such as meningitis or encephalitis Stroke Cerebral palsy Mental disabilities Seizures occurring soon after head injury Family history of epilepsy or fever-related seizures Alzheimer’s disease Lengthy febrile seizures Alcohol or drug abuse Diagnosis A doctor diagnoses epilepsy based on symptoms, physical signs , and test results such as: Electroencephalogram (EEG) CT scan (Computed Tomography) MRI (Magnetic Resonance Imaging) Proper diagnosis of both the type of epilepsy  and the type of seizures  is essential, as seizure types are often associated with specific forms of the disorder. Treatment Epilepsy may be treated with: Antiepileptic medical therapy (AEDs) Diet therapy Surgery Medical Therapy Initial treatment for most patients with multiple seizures. Not always needed for a single seizure with low recurrence risk. Controls symptoms, does not cure the condition. Prevents seizures by reducing brain cell excitability. Medication choice  depends on: Seizure type and epilepsy type Side effects Patient’s age, gender, medical history Interactions with other medications Cost Diet Therapy Used in specific forms of epilepsy: Ketogenic diet : High-fat, adequate protein, low-carb diet started in hospital. Modified Atkins diet : Less restrictive, can be started as outpatient. Both reduce seizures in about 50%  of appropriate candidates, mostly children with refractory epilepsy who are not surgical candidates. Medically-Resistant Epilepsy About 30 percent  of patients do not respond to standard therapy. These patients are treated at specialised epilepsy centres  with a multidisciplinary team  that may include: Adult and Paediatric Epileptologists Epilepsy Nurse Practitioners Neurosurgeons EEG Technicians Clinical Neuropsychologists Psychiatrists Radiologists (Neuro & Nuclear Medicine) Dietitians Neuroscience Nurses Surgical Treatment for Epilepsy Patients with refractory epilepsy  may benefit from surgery, especially if seizures come from one area of the brain. The area must be removable without major neurological damage. Pre-Surgical Evaluation Consists of: Phase I (Non-invasive) EEG Video-EEG Monitoring MRI PET scan SPECT scan Neuropsychological Evaluation Functional MRI Wada Test Results help determine if all findings point to a single seizure origin (focus). If so, surgery may be an option. Phase II (Invasive Monitoring) If more clarity is needed, involves: Subdural Electrodes Depth Electrodes StereoEEG Functional Mapping Surgical Procedures Surgical Resections Lesionectomy : Removes abnormal tissue like tumours or cavernous malformations. Lobectomy : Removes a lobe (most commonly, temporal lobe). Multilobar Resection : Removes parts of two or more lobes. Hemispherectomy : Removes or disconnects one hemisphere. Anatomic  or Functional  approaches. Surgical Disconnections Corpus Callosotomy : Cuts the connection between hemispheres to reduce spread. Multiple Subpial Transections (MST) : Disconnects neurons without removing tissue. Stereotactic Radiosurgery Focused radiation like Gamma Knife  is used for deep-seated lesions visible on MRI. Generally used when surgery is too risky. Neuromodulation Vagus Nerve Stimulation (VNS) Electrodes implanted around vagus nerve, generator placed in chest. Reduces seizures in 40–50% of patients. Palliative, improves control, rarely eliminates seizures. Responsive Neurostimulation (RNS) FDA approved in 2014 . Implanted neurostimulator records brain activity and delivers impulses to interrupt seizures. Suitable for patients with one or two focal onset zones. Rarely results in seizure freedom but improves control. Living and Coping with Epilepsy Two life-threatening risks: Tonic-clonic status epilepticus : Prolonged seizure that requires emergency treatment. SUDEP (Sudden Unexplained Death in Epilepsy) : Rare, more common in patients with frequent, uncontrolled seizures. 70–80%  of people can successfully control seizures with treatment.Some rarely think about epilepsy apart from taking medication or doctor visits. Staying well-informed , positive , and engaged  with a healthcare team is essential to leading a full, balanced life . Conclusion Epilepsy is a complex condition that requires a tailored, multidisciplinary approach to care. With proper diagnosis and treatment, many people with epilepsy can achieve excellent seizure control and lead fulfilling lives. At Singapore Brain Spine Nerves Center, our experienced team provides expert guidance and advanced treatments for epilepsy. If you or your loved one is experiencing recurrent seizures, seek professional evaluation to manage the condition effectively. References and Acknowledgements American Association of Neurological Surgeons Singapore Brain Spine Nerves Center Protocols and Information

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) What are Gliomas? Gliomas are a category of primary brain tumours that arise from glial cells, which provide support and insulation to neurons in the central nervous system. These tumours can occur in both the brain and spinal cord and are classified based on the type of glial cells involved. Gliomas are the most common type of brain tumour in adults and can range from slow-growing to highly aggressive forms. Glioma and Glioblastoma: Advances in Classification and Research In the United States, an estimated 17,000 adults will be diagnosed this year with diffuse glioma , which includes glioblastoma, astrocytoma, and oligodendroglioma . Among these, high-grade gliomas  like glioblastoma have worse prognoses. Glioblastoma is classified  based on its histological characteristics (left) as well as IDH status . “For many years, the Neuro Oncology community has observed significant variation in survival even within traditional classification groups,” said Dr Prem Pillay  from the Singapore Brain Spine Nerves Center .“This was an enormous impetus for researchers to find new markers to better characterize glioma subtypes.” In 2015, two landmark publications , including one from a team of UCSF researchers, found three new tumor markers  that reliably classified glioma patients into distinct groups with notable differences in survival, age at diagnosis, among others.² ³ 2016 World Health Organisation (WHO) Classification Update In 2016, the WHO reorganized their classification system  for adult diffuse glioma  to integrate those molecular features, in addition to others identified since then. The majority of adult diffuse glioma are now classified into the following five groups: Glioblastoma, IDH wildtype  (no mutation) Glioblastoma, IDH mutation Diffuse or anaplastic astrocytoma, IDH wildtype  (no mutation) Diffuse or anaplastic astrocytoma, IDH mutation Oligodendroglioma or anaplastic oligodendroglioma, IDH mutation with 1p19q co-deletion Categorization of adult diffuse glioma, along with characteristics for each of the five subtypes.Image credit: Figure 1 from Molinaro et al. (2019). “By better understanding glioma subtypes, we can help our patients make decisions about treatment,” said Dr Prem Pillay The Future of Brain Tumor Classification Since then, additional markers  have been identified and are in use today to further improve accuracy in prognoses for certain gliomas. A comprehensive overview of molecular features that are also associated with patient outcome and/or treatment response includes the following: TERT and ATRX mutations  affecting telomere maintenance Tumor methylation profile Methylation of the MGMT promoter CDKN2A and/or CDKN2B deletion H3 K27M mutation In the last decade, identifying such molecular features  and their associated pathways has provided mechanistic insight  into how these distinct tumor subtypes form and their potential response to targeted therapy . For instance, researchers recently identified a protein subunit  that activates mutated TERT promoters , which is currently under investigation as a potential therapeutic target. As we continue to identify additional markers, proposed changes to the WHO guidelines  remains an ongoing topic of discussion. The cIMPACT-NOW  (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy ), was created to assess and recommend regular updates to the brain tumor classification system. The discovery of molecular features to better characterize glioma subtypes  has certainly impacted the clinic and continues to shape the direction of research. “Increasingly, molecular analysis of patient samples is becoming a more widespread practice. Identifying a patient’s unique tumor profile is critical not only for diagnosis and prediction of prognoses, but potentially for tailoring treatment to the patient’s specific gene alterations” Identifying Glioma Risk Factors Another recent, significant advance in brain tumor research involves the discovery of 25 inherited variants  that increase the risk of glioma. The majority of these gene alterations are either in or near genes known to be involved in specific cancer-related pathways , providing additional insight into how gliomas develop. In contrast, recent observations suggest that a history of allergies  (or other conditions with heightened immune responses, like asthma and eczema ) is associated with decreased glioma risk . These findings have spurred additional research into characteristics of the immune system  that are involved in glioma pathogenesis and prognosis. Large-scale retrospective and prospective epidemiological studies  to characterize peripheral immune profiles  on the basis of archival DNA  are underway at UCSF to assess how variation amongst patients’ immune profiles impacts glioma risk. Together, these findings combined with the discoveries of changes within the tumors provide a solid foundation for future research into why some people get glioma  and what may be done to help reduce the risk of disease or death  from this disease. Conclusion Gliomas are a complex group of brain tumours that require specialised and multidisciplinary care. Early diagnosis and tailored treatment can significantly improve outcomes and quality of life. At Singapore Brain Spine Nerves Center , we are dedicated to providing expert care for glioma patients, leveraging advanced diagnostic and treatment options. If you or a loved one are experiencing concerning neurological symptoms, schedule a consultation today for comprehensive evaluation and guidance. References: UCSF Brain Tumor Information Cleveland Clinic Brain Tumor Information Singapore Brain Spine Nerves Center

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) Meningioma The Meningioma  is a primary intracranial tumor that is one of the most common benign tumors within the cranium (head). About 40–60% of benign tumors are meningiomas. About 15% of all primary intracranial tumors (both benign and malignant) are meningiomas. Origin:  They originate from the arachnoid cap cells that occur most often at the arachnoid granulations, which are near the midline adjacent to the superior sagittal sinus (the large midline vein of the head). Another location is the tela choroidea in the ventricles. They are therefore intracranial but not intracerebral  (within the head but not in the brain). In other words, they usually occur from the covering of the brain called the dura and not from within the brain. Epidemiology and Characteristics Age:  The peak age is from 40 to 60 years. Sex:  It is more common in females than males. Genetics:  72% of tumors have monosomy 22. Risk factors:  Previous radiation, neurofibromatosis type 2 (NF2). Locations: Cranial (within the head): 90% Spinal canal: 9% Others (neck, parotid, etc.): 1% About 50% are parasagittal and convexity (near the midline and over the lobes of the brain). Grading:  WHO classification I, II, III – from the least to the most aggressive. Pathology:  Meningothelial, fibroblastic, psammomatous, angiomatous, and transitional (most common). Aggressive variants:  They invade the brain, have necrosis, mitosis, papillary features, or are locally recurrent. Malignant:  As above, with metastases. Clinical Features They may be symptomatic or asymptomatic  at the time of discovery.Usual symptoms may include: Headaches Seizures Loss of any of the senses (smell, taste, hearing, vision, sensation) Motor weakness (hemiparesis) Memory loss Language problems (dysphasia, aphasia) Some people with these tumors are mistakenly diagnosed with dementia, strokes, or psychiatric problems . Diagnostic Tests This includes a thorough neurological examination  followed by brain scanning. In emergencies, a CT of the brain with contrast  can be done quickly. An MRI of the brain with gadolinium  is the definitive test. The appearance of a meningioma on these tests is usually unique or characteristic enough for an accurate diagnosis most of the time.There are exceptions where a biopsy with tissue examination  is still needed. Biopsy A biopsy is not mandatory  for the diagnosis of a meningioma. MRI with gadolinium and CT of the brain  can be fairly clear in determining the diagnosis of a meningioma.The presence of an intracranial but extracerebral enhancing tumor with a dural tail  is a classical finding. A biopsy can be done by: Stereotactic computer-aided biopsy , where a needle is guided to the tumor after detailed computer planning based on pre-surgical imaging and using a stereotactic frame. Frameless stereotaxis , using a system like the StealthStation  or Robotic Guidance . Surgery Microsurgery  using a high-definition microscope and microinstruments is the latest type of surgery for meningiomas. CAN/CAM (Computer Aided Neurosurgery / Computer Aided Microsurgery)  and VR technology  can also be used. Lasers, “Super-Lasers”, CUSAs / Ultrasonic beams, the Malis technique  can be used for tumor removal.The StealthStation  and other neuro-navigation systems  are useful in allowing a minimally invasive approach  in the removal of these tumors. Radiosurgery Radiosurgery refers to computer-planned, accurately focused high energy beams  used for non-invasive tumor treatment. Radiosurgery has been shown to be effective for meningiomas.Modern systems include: Gamma Knife Novalis systems with Photon Beams Proton Beam Treatment methods: Single session Multiple sessions : Known as SRT (stereotactic radiation therapy)  or FSR (fractionated stereotactic radiosurgery) New forms include MicroRadiosurgery  and Proton Beam Therapy . Combined Treatment Combined Microsurgery and Radiosurgery (CMR)  uses both modalities for treating large, difficult-to-remove, or dangerously located meningiomas.This can be a lower risk protocol  for complete tumor removal, especially in higher risk patients . Recent Advances Molecular Profiling Molecular profiling has revolutionised meningioma diagnosis and classification. The 2021 WHO classification  now incorporates molecular features alongside histological grading. Key molecular alterations include: NF2 mutations : Found in ~60% of sporadic meningiomas TRAF7, KLF4, AKT1, SMO mutations : Common in non-NF2 mutated meningiomas SMARCE1 mutations : Associated with clear cell meningiomas BAP1, SMARCB1 mutations : Linked to high-grade meningiomas DNA methylation profiling  helps identify clinically relevant subgroups beyond traditional histological grading. Neuroimaging Recent imaging advances include: Arterial spin labelling and dynamic susceptibility contrast-enhanced MRI : Assess tumor vascularity and guide preoperative embolisation. MR spectroscopy and PET-MRI : Help distinguish meningiomas from malignant mimics. Perfusion imaging : Provides insight into tumor grade and recurrence potential. Machine learning algorithms : Predict tumor consistency and behaviour based on imaging features. Treatment Advances Surgical Approaches Minimally invasive techniques Endoscopic and keyhole approaches reduce morbidity and improve cosmetic results. Intraoperative imaging and navigation Enhance resection while preserving critical structures. Fluorescence-guided surgery Techniques like 5-ALA fluorescence  help visualise tumour margins. Radiation Therapy Stereotactic radiosurgery (SRS) Increasingly used for small to medium-sized tumors, especially near eloquent areas. Fractionated stereotactic radiotherapy (FSRT) Offers precision for larger tumors or those near critical structures. Proton beam therapy Reduces radiation exposure to surrounding healthy tissue. Systemic Therapies Although systemic therapies have shown limited historical efficacy, new developments include: Targeted therapies Inhibitors of molecular pathways (e.g., mTOR, VEGF, SMO) are in trials. Immunotherapy Checkpoint inhibitors and immunomodulatory treatments under investigation, especially for high-grade meningiomas. Peptide Receptor Radionuclide Therapy (PRRT) PRRT  is emerging as a treatment for refractory meningiomas: A Phase II trial using 177LD  showed 78% of patients were progression-free at 6 months. It targets somatostatin receptors , highly expressed in meningiomas. Personalised Meningioma Therapy The integration of molecular profiling and imaging supports personalised treatment strategies : Risk stratification Molecular features help identify high-risk patients and guide adjuvant therapy. Treatment selection Some molecular subtypes may respond differently to therapies. Latest Research Research areas showing promise: Liquid biopsy techniques Non-invasive methods for tumor characterization and monitoring are under investigation. Novel targeted therapies targeting specific molecular alterations (e.g., NF2 pathway inhibitors) are in development. Artificial intelligence Machine learning algorithms may enhance diagnosis, treatment planning, and outcome prediction. Conclusions The field of meningioma diagnosis and treatment is rapidly evolving. Molecular profiling and advanced imaging techniques are refining our ability to classify and prognosticate these tumors. While surgery and radiation therapy remain the mainstays of treatment, emerging targeted therapies and innovative approaches like PRRT offer new options for patients with refractory disease. As our understanding of meningioma biology deepens, the path towards truly personalized treatment strategies becomes clearer, holding the promise of improved outcomes for patients with these challenging tumors.

What are Pineoblastomas? Pineoblastomas is a pineal region tumor that are best thought of as primitive neuroectodermal tumors (PNET) located in the pineal region and thus they closely resemble (both on imaging and on histology) medulloblastomas, retinoblastomas and supratentorial PNETs. Epidemiology Median age at diagnosis of 5.5 years 1). Pineoblastomas are the most agressive pineal parenchymal tumour and account for a substantial proportion of such tumours (24-50%). They are typically found in young children, with both sexes being equally affected (in contrast to the male predominance seen in pineal germinomas). There is a well established association with hereditary retinoblastomas. Patients with hereditary (bliateral) retinoblastoma 5-15% develop midline (suprasellar or pineal) neuroblastic tumours. Such cases are sometimes referred to as trilateral retinoblastoma. Clinical features Pineoblastomas are typically large and almost always associated with obstructive hydrocephalus, due to compression on the aqueduct. Compression of the tectal plate may also result in the Parinaud syndrome. Pathology The tumour originates from neuroectodermal cells. It is the least differentiated pineal cell tumours, with pineocytomas and pineal parenchymal tumour with intermediate differentiation representing better differentiated tumours along the same spectrum. Pineoblastomas are considered WHO grade IV tumours. The tumours are composed of tightly packed small round blue cells (high nuclear to cytoplasmic ratio) which in turn determines their imaging appearances Diagnosis Radiographic features Pineoblastomas tend to be large poorly defined masses, with frequent CSF seeding at presentation. They have a tendency to directly involve adjacent brain structures, which helps distinguish them from other pineal tumours which tend to be better circumscribed. Computed Tomography ( CT ) Scan The solid component tends to be slightly hyperdense compared to adjacent brain due to high cellularity. This is a characteristic shared by other small round blue cell tumours such as PNET and medulloblastoma. Classically, they are described as having peripherally disperse or “exploded” calcification (Mnemonic: blasted calcification), similar to pineocytomas. In contrast pineal germinomas tend to engulf pineal calcification. Magnetic Resonance Imaging ( MRI ) Scan Pineoblastomas tend to appear as sizable (>4 cm) irregular masses often with evidence of invasion into adjacent brain 6,9. Typical signal characteristics include : T1: isointense to hypointense to adjacent brain T2 isointense to adjacent brain areas of cyst formation or necrosis may be present T1 C+ (Gd): vivid heterogenous enhancement DWI/ADC restricted diffusion due to dense cellular packing ADC values are typically ~400-800 mm2/s ADC values can aid in differentiation of pineoblastoma/PNET from germ cell tumors in a population of children with pineal masses 2). Central necrosis is sometimes present which can make the mass appear centrally cystic and thus can roughly mimic a pineal cyst, although the latter should have a smooth thin wall Screening of the whole neural axis is necessary as CSF seeding is seen in 45% of cases. Differential diagnosis General imaging differential considerations include: other pineal parenchymal tumours pineocytoma: mature well-differentiated tumor: smaller and better circumscribed pineal parenchymal tumour with intermediate differentiation papillary tumour of the pineal region germ cell tumours germinoma marked male predominance engulfed calcification ADC values are typically much higher (~1000-2000 mm2/s 7) embryonal carcinoma choriocarcinoma teratoma: may contain fat pineal cyst thin (<2mm) wall astrocytoma of pineal gland metastasis medulloblastoma Imaging is very similar located in the vermis rather than pineal region but can be difficult to distinguish if very high in the vermis and very large Treatment Treatment is usually a combination of surgery including Stereotactic Image guided Biopsy, VP shunting or endoscopic third ventriculostomy -for hydrocephalus; Microsurgery for tumor removal, chemotherapy and radiation including Stereotactic Radiotherapy and Proton therapy stated Dr Prem Pillay , a Neurosurgeon who specializes in treating Pineal tumors including Pineoblastoma (He is currently Medical Director of the Singapore Brain Spine Nerves Center and was previously Chief Resident in Neurosurgery at the Cleveland Clinic, USA and fellow at MD Anderson Cancer Center and the Hospital for Sick Children, Toronto). Outcome They are the most aggressive and highest grade tumour among pineal parenchymal tumours. Prone to CSF seeding, which is present in 15% of patients at the time of diagnosis. Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma 3). The role of surgery and adjuvant radiotherapy on overall survival remains to be defined 4). Case series A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate the prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics. Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880). Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma 5). Using the Surveillance, Epidemiology, and End Results (SEER) cancer registry, Selvanathan et al., investigated clinical and pathological factors associated with outcome in paediatric pineoblastomas. Paediatric patients (< 16 years old) with pineoblastomas diagnosed between 1990 and 2007 were identified from the SEER database. Kaplan-Meier survival analysis and Cox models were used to examine the effect of variables on overall survival. The variables analysed included patient’s age at diagnosis, gender, race, tumour spread and size, surgical resection and the use of adjuvant radiotherapy. Seventy-eight patients were identified from the database. Twelve patients were excluded as 11 had no surgery and one patient was excluded as the surgical status was unknown. Analysis of the remaining 66 patients revealed a median age at diagnosis of 5.5 years. Three patients underwent biopsy. Seventeen patients underwent full and partial resection, respectively. A further 46 patients underwent surgery the nature of which was not recorded. Thirty-nine patients (59.1%) received adjuvant radiotherapy. Eight patients (12.1%) had both surgery (full or partial resection) and radiotherapy. The median overall survival was 40.5 months. Univariate analysis demonstrated that older age at diagnosis was the only positive predictor of overall survival. This study represents the largest analysis of paediatric pineoblastomas to date. The only clinically relevant prognostic factor was older age at diagnosis. The role of surgery and adjuvant radiotherapy on overall survival remains to be defined 6). Conclusion Pineoblastoma, though rare and aggressive, can be managed effectively with early diagnosis and a tailored treatment plan. At Singapore Brain Spine Nerves Center, we are dedicated to providing expert, compassionate care for patients facing complex conditions like pineoblastoma. If you or a loved one are experiencing concerning neurological symptoms, seek professional medical evaluation promptly. Early intervention is crucial to achieving the best possible outcomes. Visit the Singapore Brain Spine Nerves Center for comprehensive support and personalised treatments. References 1) , 4) , 6) Selvanathan SK, Richards O, Alli S, Elliott M, Tyagi AK, Chumas PD. Outcome and prognostic features in paediatric pineoblastomas: analysis of cases from the Surveillance, Epidemiology, and End Results registry (1990-2007). Acta Neurochir (Wien). 2019 May 18. doi: 10.1007/s00701-019-03909-1. [Epub ahead of print] PubMed PMID: 31104125. 2) Choudhri AF, Whitehead MT, Siddiqui A, Klimo P Jr, Boop FA. Diffusion characteristics of pediatric pineal tumors. Neuroradiol J. 2015 Apr;28(2):209-16. doi: 10.1177/1971400915581741. Epub 2015 May 11. PubMed PMID: 25963154. 3) , 5) Jin MC, Prolo LM, Wu A, Azad TD, Shi S, Rodrigues AJ, Soltys SG, Pollom EL, Li G, Hiniker SM, Grant GA. Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma. Neurosurgery. 2020 Feb 28. pii: nyaa023. doi: 10.1093/neuros/nyaa023. [Epub ahead of print] PubMed PMID: 32110805.

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) Medulloblastoma Medulloblastoma (MB) is an embryonic tumor of the neuroepithelial tissue and the most frequent primary pediatric solid malignancy. MB represents a heterogeneous group of cerebellar tumors characterized clinically by increased intracranial pressure and cerebellar dysfunction, with the most common presenting symptoms being headache, vomiting, and ataxia. Epidemiology MB is the most common malignant brain tumor in childhood. Annual incidence is estimated at 1/909,000 in Europe, 1.5/100,00 in the USA said Dr Prem Pillay , a Neurosurgeon who specializes in treating Medulloblastomas ( He trained at the Cleveland Clinic,USA and the Hospital for Sick Children, Toronto). Males are more affected than females. Clinic Description Age of disease onset is variable and can occur in patients ranging in age from the newborn period to adulthood (peak age at presentation is children 3-6 years, with only 25% of patients being between 15 and 44 years). The most common presenting symptoms are headache, vomiting, and ataxia. Additional features that may be observed include lethargy, motor or cranial nerve impairment, gaze palsy, visual impairment due to hydrocephalia, vertigo/hearing loss, behavioral changes/irritability, and extracranial pain (e.g. back pain in those with spinal metastases). Around 30% of pediatric cases present with metastases at diagnosis. Most metastases occur within the central nervous system by seeding via the cerebrospinal fluid (cranial or spinal), while spread to extracranial organs (e.g. bone marrow, liver, lungs) is very rare at diagnosis. In a minority of patients, MB is associated with Gorlin syndrome, familial adenomatous polyposis (FAP; the association of FAP and MB is referred to as the Turcot syndrome with polyposis) or with Li-Fraumeni Syndrome (see these terms). Increased susceptibility to certain tumors (neuroblastoma), hematological malignancies (acute lymphoblastic leukemia, acute myeloid leukemia) or disorders caused by mutations in genes encoding components of the RAS signaling pathway (Noonan syndrome or neurofibromatosis-Noonan syndrome) have been reported in MB (see these terms). Etiology and Molecular Genetics To date, the exact etiology of MB is still unknown but genomic data has identified multiple candidate genes that contribute to the pathogenesis of different subgroups of MB. This includes an inhibitor of the sonic hedgehog pathway SUFU (10q24.32), the RNA helicase DDX3X (Xp11.3-p11.23), chromatin regulators KDM6A (Xp11.2) and N-CoR complex genes BCOR (Xp11.4), and the Parkinson’s disease genes KMT2D (12q13.12), SMARCA4 (19p13.3), MYCN (2p24.3), and TP53 (17p13.1). Diagnostic Methods MB occurs in the vermis and 20% occurs in the hemispheres of the cerebellum. Histologically, MB is characterized by small, round cells that stain blue with haematoxylin spectrum and appearance ranges from tumors with extensive nodularity to those with large cell/anaplastic features. Apart from classical MB, four histological variants of MB are recognized: anaplastic MB, large cell MB, MB with extensive nodularity, and desmoplastic/nodular MB. Differential diagnosis Differential diagnosis includes other brain tumors (ependymoma, glial tumor, atypical teratoid rhabdoid tumor; see these terms) and other causes of cerebellar alterations (infectious or cystic lesions, hemorrhages). Management and treatment Initially, patients need to be checked for increased intracranial pressure. The best current treatment is gross total resection of the Tumor using Microsurgery assisted with Computer aided Image guided technology, Ultrasonic tumor removal systems, Lasers, Microinstruments with Neuromonitoring particularly of brainstem signals followed by good ICU care stated Dr Prem Pillay who specializes in brain tumors including Medulloblastomas. The postoperative treatment depends on age, histological variant, and result of staging assessments. In children older than 3-5 years, craniospinal irradiation including Stereotactic Radiotherapy with MicroMLC technology can be applied. In younger children, brain sparing therapies avoiding irradiation can be administered in very specific constellations. Latest Advances Advances in Diagnosis : Molecular Subgrouping One of the most significant advances in medulloblastoma diagnosis has been the identification and characterization of molecular subgroups. Medulloblastomas are now classified into four main subgroups based on their molecular profiles: WNT SHH (Sonic Hedgehog) Group 3 Group 4 This classification has important implications for prognosis and treatment planning. For example, WNT tumors generally have the best prognosis, while Group 3 tumors tend to have the worst outcomes.Improved Imaging Techniques Improved Imaging Techniques Researchers are developing new imaging methods to diagnose and monitor medulloblastomas more accurately. A recent study demonstrated that combining MRI scanning with machine learning could potentially identify medulloblastoma subtypes without the need for invasive biopsies. This approach could significantly reduce diagnostic wait times from 3-4 weeks to just 10 minutes.Liquid Biopsies Liquid Biopsies Ongoing research is exploring the use of liquid biopsies (analyzing tumor DNA in cerebrospinal fluid, or blood ) to diagnose and monitor medulloblastomas non-invasively. This technique could provide real-time information about tumor genetics and treatment response. Advances in Treatment : Risk Adapted Therapy Treatment protocols are increasingly tailored based on both clinical risk factors and molecular subgroup. This approach allows for de-escalation of therapy in lower-risk patients to reduce long-term side effects, while maintaining or intensifying treatment for high-risk groups. Reduced Radiation Therapy For standard-risk patients, reducing craniospinal irradiation (CSI) from 36 Gy to 23.4 Gy, combined with oral and iv anti tumor agents , has shown similar survival outcomes with potentially fewer cognitive side effects. However, further reduction to 18 Gy resulted in poorer outcomes, particularly for Group 4 tumors. Proton Beam Therapy The use of proton beam therapy for CSI and tumor bed boost is becoming more common. This technique can deliver precise radiation doses while sparing surrounding healthy tissue, potentially reducing long-term side effects. Novel Chemotherapy Approaches Recent studies have explored new chemotherapy regimens and timing: The addition of a radiosensitizer showed improved outcomes for Group 3 patients in a post-hoc analysis of the ACNS0332 study Neoadjuvant anti tumor agents before surgery is being investigated to potentially improve surgical outcomes and neuropsychological function Immunotherapy Several immunotherapy approaches are being studied for medulloblastoma: Adoptive T-cell therapy combined with PD-1 inhibitors is being tested in a clinical trial for relapsed Group 4 medulloblastoma An mRNA cancer vaccine is being developed to reprogram the immune system to attack medulloblastoma cells Targeted Therapies Researchers are identifying new molecular targets for medulloblastoma treatment: An anti tumor agent originally developed for pancreatic cancer has shown promise in preclinical models of Group 3 medulloblastoma Targeting specific regions of the EP300/CBP proteins, particularly the bromodomain, has demonstrated anti-tumor activity in Group 3 medulloblastoma cells Infant Treatment Protocols For infants (typically defined as under 4 years old), treatment approaches aim to delay or avoid radiation therapy due to its severe cognitive effects. Current strategies include: High-dose anti tumor agents with stem cell rescue Intrathecal and intravenous anti tumor agents Combinations of these approaches Future Directions Further refinement of molecular subgrouping and identification of targetable mutations within subgroups. Development of more effective and less toxic targeted therapies. Optimization of immunotherapy approaches for medulloblastoma. Improvement of treatment strategies for infants and young children to minimize long-term cognitive effects. Integration of liquid biopsy techniques for real-time monitoring of treatment response and tumor evolution. These advances in diagnosis and treatment offer hope for improved outcomes and quality of life for patients with medulloblastoma and other PNETs. However, continued research is needed to address the challenges posed by these aggressive pediatric brain tumors. *The Hospital for Sick Children Toronto, Canada is one of the leading Pediatric and Childrens Cancer Centers in the world including for the treatment of Pediatric Brain Tumors. MD Anderson is one of the leading Cancer Centers in the USA and Globally. Conclusion Medulloblastoma and PNET are challenging tumours that require prompt and expert care. Early diagnosis and a multidisciplinary treatment approach are essential for improving outcomes and quality of life. If you or a loved one experiences persistent neurological symptoms seek immediate evaluation. Visit the Singapore Brain Spine Nerves Center for specialised care and support.

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) What Are Primary Central Nervous System (CNS) Lymphoma ? Primary Central Nervous System (CNS) Lymphoma is a malignant, or high-grade brain tumor of B cell origin. A CNS Lymphoma can occur in both immuno-competent patients as well as patients with immunodeficiency (eg. HIV positive). Who Gets Affected? Age/Sex:  The mean age is about 50 years except for HIV+ve or immuno-deficient patients who are mostly in the late 20s. What Brings Them to the Clinic? Presentation:  Headaches, seizures, blurred vision, cranial neuropathy and focal neurological symptoms (hemiparesis, aphasia etc). How is It Diagnosed? Diagnosis: MRI is the diagnostic modality of choice. The tumor shows intense contrast enhancement with gadolinium. The lesions are usually cerebral and single in about 2/3rds of patients. HIV+ve patients usually have multiple lesions. The use of steroids prior to imaging may cause the lesion to temporarily disappear, hindering diagnosis. Stereotactic Biopsy or Image-guided craniotomy and biopsy is usually needed for histopathological diagnosis. The therapeutic role of aggressive surgical resection is limited. What Are the Treatment Options? Treatment:  Image-guided /Computer-aided Craniotomy and aggressive tumor resection is rarely done as it can make patients worse and does not have a major impact on survival. The exception is for large tumors with mass effect and impending herniation. Radiation has an important role as primary CNS lymphoma is very radiosensitive. Stereotactic radiation and NeuroTomotherapy are more advanced forms of radiation. Chemotherapy especially intrathecal chemotherapy through an Ommaya reservoir is a mainstay of treatment. MTX (methothrexate) is the agent of choices. Conclusion Primary CNS lymphoma is a rare yet aggressive condition requiring timely diagnosis and specialised treatment. If you or a loved one experiences persistent neurological symptoms, it is crucial to seek medical attention immediately. At Singapore Brain Spine Nerves Center, our experienced team is dedicated to providing comprehensive and personalised care for patients with primary CNS lymphoma. Contact us today for expert consultation and compassionate support.

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology (Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA) Craniopharyngiomas are benign brain tumors (not a cancer). They can affect children and adults. Craniopharyngiomas usually grow near the base of the brain, just above the pituitary gland. The pituitary gland makes hormones that control important body functions. Craniopharyngiomas do not usually spread. Because they grow close to the pituitary gland, they can cause changes in the way that it works. Symptoms of craniopharyngiomas include: changes in hormone levels. In adults this might cause difficulty getting an erection and irregular periods. It can also cause growth problems in children and diabetes loss of eyesight headaches a build up of pressure in and around the brain, which can cause feeling or being sick Symptoms can develop suddenly, which means that you feel unwell quickly or they can develop more slowly. How common it is Craniopharyngiomas are not common tumors. In children, between 6 and 13 out of every 100 brain tumors (6 to 13%) are craniopharyngiomas. And in adults, between 1 and 3 out of every 100 brain tumors (1 to 3%) are craniopharyngiomas. What tests will I have? To find out what is causing your symptoms our Neurosurgeon will arrange for you to have some tests. The tests you might have include: blood tests to look at the levels of hormones MRI brain scan or CT brain scan eye examinations including Fundal examination of the optic nerve a biopsy As well as finding out whether you have a tumor, the tests check the size of the tumor and its location. Treatment According to Dr Prem Pillay a Singapore Neurosurgeon, (trained at the Cleveland Clinic -USA,MD Anderson Cancer Center-USA and the Hospital for Sick Children, Toronto) an expert on Craniopharyngiomas, microsurgery either through a craniotomy or through Endoscopic surgery through the nose to attempt complete tumor removal is usually recommended. In patients where the tumor cannot be completely removed safely or where patients decline surgery Radiotherapy especially more advanced methods like Stereotactic Radiotherapy using Micro MLC technology or Radiosurgery can be used. Proton Therapy is another advanced technology that can be used. Hormone replacement therapy may be needed if there are changes in the levels of hormones. Surgery Specifics A brain specialist surgeon (neurosurgeon) removes all the tumor or just a part depending on where the tumor is. Some tumors are close to important parts of the brain such as the optic nerve and the hypothalamus. These tumors cannot usually be completely removed. The side effects you might have after the operation include: changes in the hormone levels high blood sugar levels (diabetes) changes in vision weight gain behaviour changes Radiotherapy If there is residual tumor you may have Stereotactic radiotherapy after surgery. This is to try to stop the tumor from coming back. You might also have radiotherapy if the tumor comes back. For small tumors, you might have stereotactic radiotherapy or radiosurgery. Both treatments target high doses of radiotherapy to the tumor. Some people may also have a type of radiotherapy called proton beam therapy. It uses high energy or low energy proton beams to the tumor. Hormone replacement Many people with a craniopharyngioma have changes in their hormone levels. This is due to either the tumor itself or as a side effect of treatment. You might need to take hormone replacement therapy to help with this. The type of hormone you take depends on your individual needs. Follow up You have regular appointments with your doctor after treatment finishes. Your doctor examines you at each appointment. They ask how you are feeling, whether you have had any symptoms or side effects and if you are worried about anything. You might also have MRI scans on some visits. How often you have check ups depends on your individual situation. Most people have a check up every 6 to 12 months, for up to 5 years. Coping with craniopharyngioma Coping with a diagnosis of a brain tumor can be difficult, both practically and emotionally. It can be especially difficult when you have a uncommon tumor. Being well informed about the type of tumor you have, and its treatment can make it easier to cope. Craniopharyngiomas are rare malformational tumours of low histological malignancy arising along the craniopharyngeal duct. The two histological subtypes, adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP), differ in genesis and age distribution. ACPs are diagnosed with a bimodal peak of incidence (5–15 years and 45–60 years), whereas PCPs are restricted to adults mainly in the fifth and sixth decades of life. ACPs are driven by somatic mutations in CTNNB1 (encoding β-catenin) that affect β-catenin stability and are predominantly cystic in appearance. PCPs frequently harbour somatic BRAFV600E mutations and are typically solid tumours. Clinical manifestations due to increased intracranial pressure, visual impairment and endocrine deficiencies should prompt imaging investigations, preferentially MRI. Treatment comprises neurosurgery and radiotherapy; intracystic chemotherapy is used in monocystic ACP. Although long-term survival is high, quality of life and neuropsychological function are frequently impaired due to the close anatomical proximity to the optic chiasm, hypothalamus and pituitary gland. Indeed, hypothalamic involvement and treatment-related hypothalamic lesions frequently result in hypothalamic obesity, physical fatigue and psychosocial deficits. Given the rarity of these tumours, efforts to optimize infrastructure and international collaboration should be research priorities. Dr Prem Pillay a Neurosurgeon who specializes in the treatment of these brain tumors agrees and notes that advances in Neurosurgery and Neurosciences including Molecular biology and Genetics will help achieve better results for those with this disease. Conclusion Craniopharyngiomas, though benign, can have profound effects on health due to their location and potential to disrupt critical brain functions. Early diagnosis and a multidisciplinary approach to treatment are key to optimising outcomes. If you or your loved one is experiencing symptoms suggestive of a brain tumour, seek medical advice promptly. Visit the Singapore Brain Spine Nerves Center for expert care tailored to your needs and a comprehensive treatment plan designed for your journey to recovery. References Singapore Brain Spine Nerves Center Protocols and information Cancer UK information