Lecture 26 - 28-Neuronal disorders.pdf

NEUROLOGICAL AND PSYCHIATRIC DISORDERS In memory MIGRAINE HEADACHE § A patient presents to her primary care provider at the clin with a “pounding and throbbing” Headache. The third of its kind within the past month. Her pain is centralized in the right temple. She also complains of neck pain....

NEUROLOGICAL AND PSYCHIATRIC DISORDERS In memory MIGRAINE HEADACHE § A patient presents to her primary care provider at the clin with a “pounding and throbbing” Headache. The third of its kind within the past month. Her pain is centralized in the right temple. She also complains of neck pain. § Approximately 4% of adults experience headaches nearly every day. Migraine and tension-type headaches are common headache disorders in clinic and result in significant reduction in social activities and work capacity of the suffers (Woolhouse, 2005). § Migraine is in essence a familial episodic disorder whose key marker is headache, with certain associated features § Migraine is a form of sensory processing disturbance with wide ramifications for central nervous system function, and while pain is used as the exemplar symptom, a braincentered explanation provides a framework to understand all the manifestations of migraine § Genetics play a big role in migraine. This means that it is often inherited in families. It is estimated that up to 60% of the reason people get migraine is because of their genes. These genes make people more sensitive to changes in their environment such as lifestyle factors and triggers that can bring on an attack. § In approximately 50% of the reported families, Familial hemiplegic migraine (FHM) has been assigned to chromosome 19p13. § The biological basis for the linkage to chromosome 19 is mutations involving the Cav2.1 (P/Q) type voltage-gated calcium channel CACNA1A gene § According to the National Institute of Health, bio-medicine holds numerous approaches to treating Chronic Migraine. These treatments include: § the use of non-steroidal anti-inflammatory drugs (NSAIDs), § analgesic medication, § deep breathing exercises, § yoga, § and nerve block injection. While there have been research studies associating acupuncture to Chronic Migraine distinctively, there are extensive studies validating the effectiveness of acupuncture for pain, frequency, and duration of the Migraine attacks. § Pyogenic meningitis, also referred as bacterial meningitis, is a life-threatening CNS infectious disease affecting the meninges, with elevated mortality and disability rates. § Three bacteria (Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis) account for the majority of cases. § Meningitis is an inflammation of the fluid and membranes (meninges) surrounding your brain and spinal cord. § The swelling from meningitis typically triggers signs and symptoms such as headache, fever and a stiff neck. § Most cases of meningitis in the United States are caused by a viral infection, but bacterial, parasitic and fungal infections are other causes. Some cases of meningitis improve without treatment in a few weeks. Others can be life-threatening and require emergency antibiotic treatment. § Seek immediate medical care if you suspect that someone has meningitis. Early treatment of bacterial meningitis can prevent serious complications. § Sudden high fever § Stiff neck § Severe headache that seems different from normal § Headache with nausea or vomiting § Confusion or difficulty concentrating § Seizures § Sleepiness or difficulty waking § Sensitivity to light § No appetite or thirst § Skin rash (sometimes, such as in meningococcal meningitis) § Fever and nuchal rigidity may be absent or mild in immunocompromised or older patients and in alcoholics. § Often, in older patients, the only sign is confusion in those who were previously alert or altered responsiveness in those who have dementia. In such patients, as in neonates, the threshold for doing lumbar puncture should be low. § Brain imaging (MRI or, less optimally, CT) should be done if focal neurologic deficits are present or increased ICP is suspected. § If bacterial meningitis develops after a neurosurgical procedure, symptoms often take days to develop. § Bacteria that enter the bloodstream and travel to the brain and spinal cord cause acute bacterial meningitis. § But it can also occur when bacteria directly invade the meninges. This may be caused by an ear or sinus infection, a skull fracture, or — rarely — some surgeries. § This bacterium is the most common cause of bacterial meningitis in infants, young children and adults in the United States. It more commonly causes pneumonia or ear or sinus infections. A vaccine can help prevent this infection. § This bacterium is another leading cause of bacterial meningitis. These bacteria commonly cause an upper respiratory infection but can cause meningococcal meningitis when they enter the bloodstream. This is a highly contagious infection that affects mainly teenagers and young adults. It may cause local epidemics in college dormitories, boarding schools and military bases. A vaccine can help prevent infection. Even if vaccinated, anybody who has been in close contact with a person with meningococcal meningitis should receive an oral antibiotic to prevent the disease. § Haemophilus influenzae type b (Hib) bacterium was once the leading cause of bacterial meningitis in children. But new Hib vaccines have greatly reduced the number of cases of this type of meningitis. § If findings suggest acute bacterial meningitis, routine tests include § CSF analysis § Complete blood count and differential § Metabolic panel § Blood cultures plus polymerase chain reaction (PCR), if available § Typical CSF findings in bacterial meningitis include the following (see table CSF Findings in Meningitis): § Increased pressure § Fluid that is often turbid § A high WBC count (consisting predominantly of polymorphonuclear neutrophils) § Elevated protein § A low CSF: blood glucose ratio § Cerebrospinal fluid (CSF) analysis § As soon as acute bacterial meningitis is suspected, blood cultures and lumbar puncture for CSF analysis (unless contraindicated) are done. Blood should be analyzed when lumbar puncture is done so that blood glucose levels can be compared with CSF glucose levels. Treatment should be started as follows: § If bacterial meningitis is suspected and the patient is very ill, antibiotics and corticosteroids are given immediately, even before lumbar puncture. § If bacterial meningitis is suspected and lumbar puncture will be delayed pending CT or MRI, antibiotics and corticosteroids should be started after blood cultures but before neuroimaging is done; the need for confirmation should not delay treatment. AUTISM SPECTRUM DISORDER § Speech language pathologist description: § Mitch had trouble making eye contact with listeners. His expressive language was vague: his sentences were long enough and had the right grammar and syntax (word order) but the words he chose did not quite communicate his meaning and the listener had to work extra hard at decoding the message. § It was hard to have a conversation with Mitch: he tended to monopolize the taking, worked hard to steer it toward one of his favorite subjects and did not appear to be listening when it was the other person’s turn to talk. § He had trouble with focus and attention: he was quite distractible. He had two favorite subject (farm tractors and the carved images at Mt. Rushmore) and didn’t really talk much about anything else. § He did not play very much with other children at school or in the neighborhood and interacted mainly with adults. § Mitch periodically had bouts of anxiety and if was much harder for him to focus when that was happening. In speech therapy, among other objectives, we practiced looking at the listener and using just exactly the right word(s) to answer questions § Autism spectrum disorder (ASD) is a developmental disability that can cause significant social, communication and behavioral challenges. There is often nothing about how people with ASD look that sets them apart from other people, but people with ASD may communicate, interact, behave, and learn in ways that are different from most other people. The learning, thinking, and problem-solving abilities of people with ASD can range from gifted to severely challenged. § Some people with ASD need a lot of help in their daily lives; others need less. § A diagnosis of ASD now includes several conditions that used to be diagnosed separately: autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS), and Asperger syndrome. These conditions are now all called autism spectrum disorder. https://www.cdc.gov/ncbddd/autism/facts .html § People with ASD often have problems with social, emotional, and communication skills § Children or adults with ASD might: § not look at objects when another person points at them § avoid eye contact and want to be alone § have trouble understanding other people’s feelings or talking about their own feelings § prefer not to be held or cuddled, or might cuddle only when they want to § appear to be unaware when people talk to them, but respond to other sounds § be very interested in people, but not know how to talk, play, or relate to them § have trouble expressing their needs using typical words or motions § not play “pretend” games (for example, not pretend to “feed” a doll) § repeat actions over and over again § … § Base on the behaviors § Genetic (?).. fragile X syndrome § There is currently no cure for ASD. However, research shows that early intervention treatment services can improve a child’s development. § Early intervention services help children from birth to 3 years old (36 months) learn important skills. Services can include therapy to help the child talk, walk, and interact with others. Therefore, it is important to talk to your child’s doctor as soon as possible if you think your child has ASD or other developmental problem. Environmental, biologic and genetic factors…. § Most scientists agree that genes are one of the risk factors that can make a person more likely to develop ASD. § Children who have a sibling with ASD are at a higher risk of also having ASD. § Individuals with certain genetic or chromosomal conditions, such as fragile X syndrome or tuberous sclerosis, can have a greater chance of having ASD. § When taken during pregnancy, the prescription drugs valproic acid and thalidomide have been linked with a higher risk of ASD. § There is some evidence that the critical period for developing ASD occurs before, during, and immediately after birth. § Children born to older parents are at greater risk for having ASD. § A 25-year-old university graduate female patient presented to our outpatient clinic with symptoms of not completely remitting despite a 5-year-long psychiatric treatment. She complained of not being able to express herself and being incapable of social interaction with others, and she cried during the psychiatric interview. § She felt irritable and tense for no apparent reason from time to time, could not concentrate, felt an urge to move around restlessly, did not want to go to her house, and despite her family’s objections, left the house to walk around at midnight. She said that during these periods she had higher levels of self-confidence; got more sociable with strangers; was more talkative; felt more irritable, tense, and behaved aggressively; and burst into laughter, which was quite unusual for her. § Bipolar disorder is a serious mental illness in which common emotions become intensely and often unpredictably magnified. § Individuals with bipolar disorder can quickly swing from extremes of happiness, energy and clarity to sadness, fatigue and confusion. § These shifts can be so devastating that individuals may choose suicide. § All people with bipolar disorder have manic episodes — abnormally elevated or irritable moods that last at least a week and impair functioning. But not all become depressed. § In community samples, between 0% and 2.0% of adolescents meet diagnostic criteria for BD I disorder, and between 0.1% and 0.6% meet criteria for BD II disorder § Diagnostic criteria specify that mania must last at least one week or require hospitalization. § Manic symptoms include irritability or euphoria along with symptoms such as decreased need for sleep, grandiose ideas, impulsive behavior, increased talkativeness, racing thoughts, flight of ideas, increased activity, and distractibility. § Mixed episodes include manic symptoms and simultaneous depressive symptoms lasting for at least one week. Most, but certainly not all, people with BD I experience periods of depression. § Panic disorder, § Generalized anxiety disorder, § Alcohol dependence, § And drug abuse § BD is among the most heritable of disorders. § The risk of BD among children of BD parents is four times greater than the risk among children of healthy parents. § The common susceptibility genes may predispose individuals to dopamine dysregulation and eventual psychosis. However, there are genes whose expression may affect neurodevelopment, illness-specific neurological changes, and environmental factors. § Three neurotransmitters have received the most attention in studies of mood disorders: norepinephrine, dopamine, and serotonin § Approximately 10% of people with a history of mania, one full night of sleep deprivation will trigger manic symptoms by the next morning § Neuroimaging studies indicate mood disorders are generally associated with decreased sensitivity of the serotonin receptors § In functional studies, BD I disorder is associated with elevated activity in the amygdala, a key brain structure involved in identifying the significance of emotionally relevant stimuli of both negative and positive valence. § PET studies and functional MRI studies of activity during cognitive or emotional tasks have each shown a pattern of amygdala hyperactivity among people with BD I disorder § People with BD also demonstrate diminished activity of the hippocampus and prefrontal cortex § There is five medications for BD: lithium, the traditional antipsychotic chlorpromazine (Thorazine), the anticonvulsant divalproex sodium (also known as valproate, and usually marketed as Depakote, Depakene, or Depakon), the atypical antipsychotic olanzapine (Zyprexa), and the anticonvulsant lamotrigine (Lamictal). § Pharmacological treatments for BD affect levels of dopamine and serotonin § Patient is referred to physical therapy after being involved in a motor vehicle accident (four months ago) and continuing to have ongoing pain and stiffness. § Patient is 42 years old, female, and lives alone in her apartment. She was working as a receptionist at time of accident but is not currently able to work due to pain. § Patient has a family history of rheumatoid arthritis and fibromyalgia. She has no history of significant alcohol or recreational drug use. Patient has had no past surgeries, no history of cancer. She is currently taking Prozac for her depression and anxiety. She was referred to physical therapy by her primary care physician. She has never been to physical therapy before today. § Fibromyalgia is generally considered to be a stress-related disorder that involves abnormal functioning in the hypothalamic-pituitary-adrenal (HPA) axis. § Fibromyalgia has been associated with the inability to suppress cortisol § ANS (Autonomic Nervous System) abnormalities may contribute to enhanced pain and other clinical problems associated with fibromyalgia via the alteration of physiologic responses required for effective stress management (e.g., increases in blood pressure) and pain inhibition via diminished production of growth hormone (GH) and insulin-like growth factor (IGF-1) § Patients with fibromyalgia often have problems with sleep, including nonrestorative sleep, insomnia, early morning awakening, and poor quality of sleep § Sleep disturbances may be related to the reduced energy and fatigue often found among patients with fibromyalgia. § Disturbed sleep may also contribute to enhanced pain § Fibromyalgia may also occur concurrently with chronic inflammatory diseases such as rheumatoid arthritis (RA) § first-degree relatives of RA patients, more frequently meet the diagnostic criteria for fibromyalgia or major mood disorders (bipolar disorder) § Results from several investigations indicate that a single nucleotide polymorphism (SNP) in the serotonin transporter (5-HTT) gene may contribute to enhanced pain sensitivity among patients with fibromyalgia § Another area of investigation is the relationship between catechol-O- methyltransferase (COMT) gene variants and pain. § Physical Stressors (squatting for more than 15 minutes; pulling more than 56 kg) § Psychosocial Stressors (dissatisfaction with social support from colleagues and monotonous work) ENCEPHALITIS § In acute encephalitis, inflammation and edema occur in infected areas throughout the cerebral hemispheres, brain stem, cerebellum, and, occasionally, spinal cord. Petechial hemorrhages may be present in severe infections. § Encephalitis is inflammation of the active tissues of the brain caused by an infection or an autoimmune response. The inflammation causes the brain to swell, which can lead to headache, stiff neck, sensitivity to light, mental confusion and seizures. § Encephalitis strikes 10–15 people per 100,000 each year, with more than 250,000 patients diagnosed in the last decade alone in the U.S. The condition can affect anyone, but more often occurs in younger people. § Infectious encephalitis is typically caused by a viral infection. § Vaccines for measles, mumps, rubella and chickenpox have reduced the rate of encephalitis from these diseases, but other viruses can cause encephalitis. § The most common causes of viral encephalitis are herpes simplex virus types 1 and 2, varicella zoster virus and enteroviruses, which cause gastrointestinal illness. § Encephalitis can also result from certain viruses carried by mosquitoes, ticks and other insects or animals such as: § West Nile virus § Japanese encephalitis virus § La Crosse virus § St. Louis virus § Equine viruses § Powassan virus § Zika § Chikungunya § Autoimmune encephalitis occurs when a person’s own antibodies or immune cells attack the brain. Antibodies may target specific proteins or receptors in the brain, which determine the type of autoimmune encephalitis: § In anti-NMDA receptor encephalitis, the immune system targets the NMDA receptors in the brain. § In VGKC-complex antibody encephalitis, the immune system targets the VGKC brain protein complex that includes subtypes LGI-1 and CASPR2. § GABA-A and GABA-B receptors may also be targeted. § While the causes of autoimmune encephalitis are not well understood, it can sometimes result from a tumor (benign or cancerous). Some types of autoimmune encephalitis such as acute disseminated encephalomyelitis (ADEM) are typically triggered by an infection (post-infectious encephalitis). § The viral prodrome typically consists of: § fever, § headache, § nausea and vomiting, § lethargy, § and myalgias. § Infectious encephalitis often starts with flu-like symptoms § Encephalitis caused by certain infections or autoimmune processes can show up with characteristic symptoms. § A sensation of déjà vu (the feeling that one is reliving something already experienced) is a common finding in early stages of herpes simplex virus encephalitis. § A type of autoimmune encephalitis affecting NMDA receptors can start with a flu-like illness. It can then lead to behavioral changes and unusual movement patterns affecting the mouth and face, cognitive decline and impaired function of the autonomic nervous system. § Another type of autoimmune encephalitis (LGI1) is associated with seizures or other abnormal movement of the face or arm. § Neuroimaging, such as a brain MRI or CT scan § A lumbar puncture (spinal tap) to check for signs of infection in the brain or spinal cord § Electroencephalogram (EEG) to look for seizures or specific patterns of electrical activity in the brain § Blood tests or urine and stool tests to identify organisms or antibodies responsible for an infection § Additional tests may include: § A sputum culture tests the material that is coughed up from the lungs to see if certain infections are present. § In rare cases, a biopsy of affected brain tissue may be performed to allow for examination under a microscope. § Intracranial pressure monitoring (ICP) measures the pressure inside the skull to monitor the brain swelling. § The key to surviving encephalitis is early detection and effective treatment of the underlying cause. A team of specialists working together is an important factor in optimal care. § Encephalitis treatment depends on the underlying cause and symptoms, and may include: § Antiviral medications to fight viral infections affecting the brain. § Antibiotics to address underlying bacterial infections causing encephalitis. § Immunotherapy, such as steroids, intravenous antibodies (IVIg) or plasma exchange, to address certain types of autoimmune encephalitis. § Medications or other therapies to control seizures. § A breathing tube, urinary catheter, or feeding tube may be necessary if the person’s encephalitis has caused loss of consciousness. § During the encephalitis attack, the inflamed brain tissue can suffer damage, which varies greatly between patients. In general, the brain doesn’t bounce back as quickly as other body parts such as bone, skin and muscles, but it does have some capacity to recover. § Mild cases of encephalitis are usually short and result in a full recovery. However, despite improvements in diagnosis and treatment, encephalitis still leads to death in about 10% of patients. § Survivors of severe cases of encephalitis can be left with permanent problems such as fatigue, irritability, impaired concentration, seizures, hearing loss, memory loss and blindness. § Thank you for attending the neuro lectures! § I have learned a lot with you! Thank you! § See you in the Spring! § Learning never exhausts the mind