Tag: Neurological Disorder

An Overview of Neurology

Published on by Andrew Marshall2 Comments

Introduction

Neurology (from Greek: νεῦρον (neûron), “string, nerve” and the suffix -logia, “study of”) is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the spinal cord and the peripheral nerves. Neurological practice relies heavily on the field of neuroscience, the scientific study of the nervous system.

A neurologist is a physician specialising in neurology and trained to investigate, diagnose and treat neurological disorders. Neurologists diagnose and treat myriad neurologic conditions, including stroke, epilepsy, movement disorders such as Parkinson’s disease, brain infections, autoimmune neurologic disorders such as multiple sclerosis, sleep disorders, brain injury, headache disorders like migraine, tumours of the brain and dementias such as Alzheimer’s disease. Neurologists may also have roles in clinical research, clinical trials, and basic or translational research. Neurology is a nonsurgical specialty, its corresponding surgical specialty is neurosurgery.

Refer to neurohospitalist.

Brief History

The academic discipline began between the 15th and 16th centuries with the work and research of many neurologists such as Thomas Willis, Robert Whytt, Matthew Baillie, Charles Bell, Moritz Heinrich Romberg, Duchenne de Boulogne, William A. Hammond, Jean-Martin Charcot, C. Miller Fisher and John Hughlings Jackson. Neo-Latin neurologia appeared in various texts from 1610 denoting an anatomical focus on the nerves (variably understood as vessels), and was most notably used by Willis, who preferred Greek νευρολογία.

Training

In the United States and Canada, neurologists are physicians who have completed a postgraduate training period known as residency specialising in neurology after graduation from medical school. This additional training period typically lasts four years, with the first year devoted to training in internal medicine. On average, neurologists complete a total of eight to ten years of training. This includes four years of medical school, four years of residency and an optional one to two years of fellowship.

While neurologists may treat general neurologic conditions, some neurologists go on to receive additional training focusing on a particular subspecialty in the field of neurology. These training programs are called fellowships, and are one to two years in duration. Subspecialties in the United States include brain injury medicine, clinical neurophysiology, epilepsy, neurodevelopmental disabilities, neuromuscular medicine, pain medicine, sleep medicine, neurocritical care, vascular neurology (stroke), behavioural neurology, child neurology, headache, neuroimmunology and infectious disease, movement disorders, neuroimaging, neurooncology, and neurorehabilitation.

In Germany, a compulsory year of psychiatry must be done to complete a residency of neurology.

In the United Kingdom and Ireland, neurology is a subspecialty of general (internal) medicine. After five years of medical school and two years as a Foundation Trainee, an aspiring neurologist must pass the examination for Membership of the Royal College of Physicians (or the Irish equivalent) and complete two years of core medical training before entering specialist training in neurology. Up to the 1960s, some intending to become neurologists would also spend two years working in psychiatric units before obtaining a diploma in psychological medicine. However, that was uncommon and, now that the MRCPsych takes three years to obtain, would no longer be practical. A period of research is essential, and obtaining a higher degree aids career progression. Many found it was eased after an attachment to the Institute of Neurology at Queen Square, London. Some neurologists enter the field of rehabilitation medicine (known as physiatry in the US) to specialise in neurological rehabilitation, which may include stroke medicine, as well as traumatic brain injuries.

Physical Examination

During a neurological examination, the neurologist reviews the patient’s health history with special attention to the patient’s neurologic complaints. The patient then takes a neurological exam. Typically, the exam tests mental status, function of the cranial nerves (including vision), strength, coordination, reflexes, sensation and gait. This information helps the neurologist determine whether the problem exists in the nervous system and the clinical localization. Localisation of the pathology is the key process by which neurologists develop their differential diagnosis. Further tests may be needed to confirm a diagnosis and ultimately guide therapy and appropriate management. Useful adjunct imaging studies in neurology include CT scanning and MRI. Other tests used to assess muscle and nerve function include nerve conduction studies and electromyography.

Clinical Tasks

Neurologists examine patients who are referred to them by other physicians in both the inpatient and outpatient settings. Neurologists begin their interactions with patients by taking a comprehensive medical history, and then performing a physical examination focusing on evaluating the nervous system. Components of the neurological examination include assessment of the patient’s cognitive function, cranial nerves, motor strength, sensation, reflexes, coordination, and gait.

In some instances, neurologists may order additional diagnostic tests as part of the evaluation. Commonly employed tests in neurology include imaging studies such as computed axial tomography (CAT) scans, magnetic resonance imaging (MRI), and ultrasound of major blood vessels of the head and neck. Neurophysiologic studies, including electroencephalography (EEG), needle electromyography (EMG), nerve conduction studies (NCSs) and evoked potentials are also commonly ordered. Neurologists frequently perform lumbar punctures to assess characteristics of a patient’s cerebrospinal fluid. Advances in genetic testing have made genetic testing an important tool in the classification of inherited neuromuscular disease and diagnosis of many other neurogenetic diseases. The role of genetic influences on the development of acquired neurologic diseases is an active area of research.

Some of the commonly encountered conditions treated by neurologists include headaches, radiculopathy, neuropathy, stroke, dementia, seizures and epilepsy, Alzheimer’s disease, attention deficit/hyperactivity disorder, Parkinson’s disease, Tourette’s syndrome, multiple sclerosis, head trauma, sleep disorders, neuromuscular diseases, and various infections and tumours of the nervous system. Neurologists are also asked to evaluate unresponsive patients on life support to confirm brain death.

Treatment options vary depending on the neurological problem. They can include referring the patient to a physiotherapist, prescribing medications, or recommending a surgical procedure.

Some neurologists specialise in certain parts of the nervous system or in specific procedures. For example, clinical neurophysiologists specialise in the use of EEG and intraoperative monitoring to diagnose certain neurological disorders. Other neurologists specialise in the use of electrodiagnostic medicine studies – needle EMG and NCSs. In the US, physicians do not typically specialize in all the aspects of clinical neurophysiology – i.e. sleep, EEG, EMG, and NCSs. The American Board of Clinical Neurophysiology certifies US physicians in general clinical neurophysiology, epilepsy, and intraoperative monitoring. The American Board of Electrodiagnostic Medicine certifies US physicians in electrodiagnostic medicine and certifies technologists in nerve-conduction studies. Sleep medicine is a subspecialty field in the US under several medical specialties including anaesthesiology, internal medicine, family medicine, and neurology. Neurosurgery is a distinct specialty that involves a different training path and emphasizes the surgical treatment of neurological disorders.

Also, many nonmedical doctors, those with doctoral degrees (usually PhDs) in subjects such as biology and chemistry, study and research the nervous system. Working in laboratories in universities, hospitals, and private companies, these neuroscientists perform clinical and laboratory experiments and tests to learn more about the nervous system and find cures or new treatments for diseases and disorders.

A great deal of overlap occurs between neuroscience and neurology. Many neurologists work in academic training hospitals, where they conduct research as neuroscientists in addition to treating patients and teaching neurology to medical students.

General Caseload

Neurologists are responsible for the diagnosis, treatment, and management of all the conditions mentioned above. When surgical or endovascular intervention is required, the neurologist may refer the patient to a neurosurgeon or an interventional neuroradiologist. In some countries, additional legal responsibilities of a neurologist may include making a finding of brain death when it is suspected that a patient has died. Neurologists frequently care for people with hereditary (genetic) diseases when the major manifestations are neurological, as is frequently the case. Lumbar punctures are frequently performed by neurologists. Some neurologists may develop an interest in particular subfields, such as stroke, dementia, movement disorders, neurointensive care, headaches, epilepsy, sleep disorders, chronic pain management, multiple sclerosis, or neuromuscular diseases.

Overlapping Areas

Some overlap also occurs with other specialties, varying from country to country and even within a local geographic area. Acute head trauma is most often treated by neurosurgeons, whereas sequelae of head trauma may be treated by neurologists or specialists in rehabilitation medicine. Although stroke cases have been traditionally managed by internal medicine or hospitalists, the emergence of vascular neurology and interventional neuroradiology has created a demand for stroke specialists. The establishment of Joint Commission-certified stroke centres has increased the role of neurologists in stroke care in many primary, as well as tertiary, hospitals. Some cases of nervous system infectious diseases are treated by infectious disease specialists. Most cases of headache are diagnosed and treated primarily by general practitioners, at least the less severe cases. Likewise, most cases of sciatica are treated by general practitioners, though they may be referred to neurologists or surgeons (neurosurgeons or orthopaedic surgeons). Sleep disorders are also treated by pulmonologists and psychiatrists. Cerebral palsy is initially treated by paediatricians, but care may be transferred to an adult neurologist after the patient reaches a certain age. Physical medicine and rehabilitation physicians may treat patients with neuromuscular diseases with electrodiagnostic studies (needle EMG and nerve-conduction studies) and other diagnostic tools. In the United Kingdom and other countries, many of the conditions encountered by older patients such as movement disorders, including Parkinson’s disease, stroke, dementia, or gait disorders, are managed predominantly by specialists in geriatric medicine.

Clinical neuropsychologists are often called upon to evaluate brain-behaviour relationships for the purpose of assisting with differential diagnosis, planning rehabilitation strategies, documenting cognitive strengths and weaknesses, and measuring change over time (e.g. for identifying abnormal ageing or tracking the progression of a dementia).

Relationship to Clinical Neurophysiology

In some countries such as the United States and Germany, neurologists may subspecialise in clinical neurophysiology, the field responsible for EEG and intraoperative monitoring, or in electrodiagnostic medicine nerve conduction studies, EMG, and evoked potentials. In other countries, this is an autonomous specialty (e.g. UK, Sweden, Spain).

Overlap with Psychiatry

Refer to neuropsychiatry.

In the past, prior to the advent of more advanced diagnostic techniques such as MRI some neurologists have considered psychiatry and neurology to overlap. Although mental illnesses are believed by many to be neurological disorders affecting the central nervous system, traditionally they are classified separately, and treated by psychiatrists. In a 2002 review article in the American Journal of Psychiatry, Professor Joseph B. Martin, Dean of Harvard Medical School and a neurologist by training, wrote:

“the separation of the two categories is arbitrary, often influenced by beliefs rather than proven scientific observations. And the fact that the brain and mind are one makes the separation artificial anyway”.

Neurological disorders often have psychiatric manifestations, such as post-stroke depression, depression and dementia associated with Parkinson’s disease, mood and cognitive dysfunctions in Alzheimer’s disease, and Huntington disease, to name a few. Hence, the sharp distinction between neurology and psychiatry is not always on a biological basis. The dominance of psychoanalytic theory in the first three-quarters of the 20th century has since then been largely replaced by a focus on pharmacology. Despite the shift to a medical model, brain science has not advanced to a point where scientists or clinicians can point to readily discernible pathological lesions or genetic abnormalities that in and of themselves serve as reliable or predictive biomarkers of a given mental disorder.

Neurological Enhancement

The emerging field of neurological enhancement highlights the potential of therapies to improve such things as workplace efficacy, attention in school, and overall happiness in personal lives. However, this field has also given rise to questions about neuroethics.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Neurology >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is the Pseudobulbar Affect?

Published on by Andrew MarshallLeave a comment

Introduction

Pseudobulbar affect (PBA), or emotional incontinence, is a type of neurological disorder characterised by uncontrollable episodes of crying or laughing. PBA occurs secondary to a neurologic disorder or brain injury. Patients may find themselves crying uncontrollably at something that is only slightly sad, being unable to stop themselves for several minutes. Episodes may also be mood-incongruent: a patient may laugh uncontrollably when angry or frustrated, for example. Sometimes, the episodes may switch between emotional states, resulting in the patient crying uncontrollably before dissolving into fits of laughter.

The pseudobulbar affect, also referred to as emotional lability, should not be confused with depression that stem from emotional instability – affective dysregulation – commonly seen in mental illnesses and certain personality disorders.

Signs and Symptoms

The cardinal feature of the disorder is a pathologically lowered threshold for exhibiting the behavioural response of laughter, crying, anger or all of the above. An affected individual exhibits episodes of laughter, crying, anger or a combination of these without an apparent motivating stimulus or in response to stimuli that would not have elicited such an emotional response before the onset of their underlying neurologic disorder. In some patients, the emotional response is exaggerated in intensity but is provoked by a stimulus with an emotional valence congruent with the character of the emotional display. For example, a sad stimulus provokes a pathologically exaggerated weeping response instead of a sigh, which the patient normally would have exhibited in that particular instance.

However, in some other patients, the character of the emotional display can be incongruent with, and even contradictory to, the emotional valence of the provoking stimulus or may be incited by a stimulus with no clear valence. For example, a patient may laugh in response to sad news or cry in response to stimuli with no emotional undertone, or, once provoked, the episodes may switch from laughing to crying or vice versa.

The symptoms of PBA can be severe, with persistent and unremitting episodes. Characteristics include:

  • The onset can be sudden and unpredictable, and has been described by some patients as coming on like a seizure;
  • The outbursts have a typical duration of a few seconds to several minutes; and,
  • The outbursts may happen several times a day.

Many people with neurologic disorders exhibit uncontrollable episodes of laughing, crying, or anger that are either exaggerated or contradictory to the context in which they occur. Where patients have significant cognitive deficits (e.g. Alzheimer’s) it can be unclear whether it is true PBA as opposed to a grosser form of emotional dysregulation, but patients with intact cognition often report the symptom as disturbing. Patients report that their episodes are at best only partially amenable to voluntary control, and unless they experience a severe change of mental status, as in traumatic brain injury they often have insight into their problem and judge their emotional displays as inappropriate and out of character. The clinical effect of PBA can be severe, with unremitting and persistent symptoms that can be disabling to patients, and may significantly affect quality of life for caregivers

Social Impact

While not as profoundly disabling as the physical symptoms of the most common diseases that cause it (such as ALS), PBA may significantly influence individuals’ social functioning and their relationships with others. Such sudden, frequent, extreme, uncontrollable emotional outbursts may lead to social withdrawal and interfere with activities of daily living, social and professional pursuits, and reduce overall healthcare. For example, patients with ALS and MS are often cognitively normal. However, the appearance of uncontrollable emotions is commonly associated with many additional neurological disorders such as attention deficit hyperactivity disorder, Parkinson’s disease, cerebral palsy, autism, epilepsy, and migraines. This may lead to avoidance of social interactions for the patient, which in turn impairs their coping mechanisms and their careers.

Depression

PBA may often be misdiagnosed as clinical depression or bipolar disorder; however, many clear distinctions exist.

Several criteria exist to differentiate between PBA and depression.

In depressive and bipolar disorders, crying, anger or laughter are typically indicative of mood, whereas the pathological displays of crying which occur in PBA are often in contrast to the underlying mood, or greatly in excess of the mood or eliciting stimulus. In addition, a key to differentiating depression from PBA is duration: PBA episodes are sudden, occurring in an episodic manner, while crying in depression is a more sustained presentation and closely relates to the underlying mood state. The level of control that one has over the crying, anger or other emotional displays in PBA is minimal or non-existent, whereas for those with depression, the emotional expression (typically crying) can be modulated by the situation. Similarly, the trigger for episodes of crying in patients with PBA may be nonspecific, minimal or inappropriate to the situation, but in depression the stimulus is specific to the mood-related condition. These differences are outlined in the adjacent Table.

In some cases, depressed mood and PBA may co-exist. Since depression is one of the most common emotional changes in patients with neurodegenerative disease or post-stroke sequelae, it is often comorbid with PBA. Comorbidity implies that depression is distinct from PBA and is not necessary for, nor does it exclude, a diagnosis of PBA.

Causes

The specific pathophysiology involved in this frequently debilitating condition is still under investigation; the primary pathogenic mechanisms of PBA remain controversial. One hypothesis, established by early researchers such as Wilson and Oppenheim, placed emphasis on the role of the corticobulbar pathways in modulating emotional expression in a top-down model, and theorised that PBA occurs when bilateral lesions in the descending corticobulbar tract cause failure of voluntary control of emotion, which leads to the disinhibition, or release, of laughing/crying centres in the brainstem. Other theories implicate the prefrontal cortex.

Secondary Condition

PBA is a condition that occurs secondary to neurological disease or brain injury, and is thought to result from disruptions of neural networks that control the generation and regulation of motor output of emotions. PBA is most commonly observed in people with neurologic injuries such as traumatic brain injury (TBI) and stroke, and neurologic diseases such as dementias including Alzheimer’s disease, attention deficit hyperactivity disorder (ADHD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD). It has been reported as a symptom of hyperthyroidism, Graves’ disease, or hypothyroidism in combination with depression.

PBA has also been observed in association with a variety of other brain disorders, including brain tumours, Wilson’s disease, syphilitic pseudobulbar palsy, and various encephalitides. Rarer conditions associated with PBA include gelastic epilepsy, dacrystic epilepsy, central pontine myelinolysis, olivopontinocerebellar atrophy, lipid storage diseases, chemical exposure (e.g. nitrous oxide and insecticides), fou rire prodromique, and Angelman syndrome.

It is hypothesized that these primary neurologic injuries and diseases affect chemical signalling in the brain, which in turn disrupts the neurologic pathways that control emotional expression.

Stroke

PBA is one of the most frequently reported post-stroke behavioural disorders, with a range of reported prevalence rates from 28% to 52%. The higher prevalence rates tend to be reported in stroke patients who are older or who have a history of prior stroke. The relationship between post-stroke depression and PBA is complicated, because the depressive syndrome also occurs with high frequency in stroke survivors. Post-stroke patients with PBA are more depressed than post-stroke patients without PBA, and the presence of a depressive syndrome may exacerbate the weeping side of PBA symptoms.

Multiple Sclerosis

Recent studies suggest that approximately 10% of patients with multiple sclerosis (MS) will experience at least one episode of emotional lability. PBA is generally associated with later stages of the disease (chronic progressive phase). PBA in MS patients is associated with more severe intellectual deterioration, physical disability, and neurological disability.

Amyotrophic Lateral Sclerosis

A study designed specifically to survey for prevalence found that 49% of patients with amyotrophic lateral sclerosis (ALS) also had PBA. PBA does not appear to be associated with duration of ALS. It is a symptom of ALS that many patients are unaware of and do not receive information about from their physician.

Traumatic Brain Injury

One study of 301 consecutive cases in a clinic setting reported a 5% prevalence. PBA occurred in patients with more severe head injury, and coincided with other neurological features suggestive of pseudobulbar palsy.

The Brain Injury Association of America (BIAA) indicates that approximately 80% of survey respondents experience symptoms of PBA. Results from a recent investigation estimate the prevalence of PBA associated with traumatic brain injury to exceed more than 55% of survivors.

Treatment

Education of patients, families, and caregivers is an important component of the appropriate treatment of PBA. Crying associated with PBA may be incorrectly interpreted as depression; laughter may be embarrassing, anger can be debilitating. It is therefore critical for families and caregivers to recognize the pathological nature of PBA and the reassurance that this is an involuntary syndrome that is manageable. Traditionally, antidepressants such as sertraline, fluoxetine, citalopram, nortriptyline, and amitriptyline have been prescribed with some efficacy.

Medication

Dextromethorphan hydrobromide affects the signals in the brain that trigger the cough reflex. It is used as a cough suppressant, although it can sometimes be used, medicinally, as a pain reliever, and is also used as a recreational drug.

Quinidine sulfate affects the way the heart beats, and is generally used in people with certain heart rhythm disorders. It is also used to treat malaria. Quinidine sulfate, as a metabolic inhibitor, “increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6, which catalyses a major biotransformation pathway for dextromethorphan,” enabling therapeutic dextromethorphan concentrations.

Dextromethorphan/quinidine is a combination of these two generic drugs, and is the first Food and Drug Administration (FDA)-approved drug for the treatment of PBA, approved on 29 October 2010.

In the pivotal multicentre study that led to its approval, the “Objectives…[were] to evaluate the safety, tolerability, and efficacy of two different doses of AVP-923 [Dextromethorphan/quinidine combination]…when compared to placebo.” The conditions and results of that study are as follows:

At one study site, a total of 326 participants received one of three dose options. “METHODS: In a 12-week randomized, double-blind trial, ALS and MS patients with clinically significant PBA” were given a twice-daily dose of one of the following:

  • Placebo (N=109)
  • Dextromethorphan hydrobromide 30 mg/quinidine sulfate 10 mg (N=110)
  • Nuedexta – dextromethorphan hydrobromide 20 mg/quinidine sulfate 10 mg (N=107)

283 patients (86.8%) completed the study. The number of PBA episodes (laughing, crying or aggressive outbursts) were 47% and 49% lower (based on the trial’s outcome measures), respectively, for the drug-combination options than for the placebo. The “mean CNS-LS scores” decreased by 8.2 points for both drug-combination options, vs a decrease of 5.7 points for the placebo.

Overall, the trial showed a statistically significant benefit from taking a combination of dextromethorphan and quinidine, with both dosages being safe and well tolerated. For a secondary objective measuring a participant’s “perceived health status…measuring eight health concepts: vitality, physical functioning, bodily pain, general health perceptions, physical role-, emotional role-, social role functioning, and mental health,” the higher dosage showed improvement, especially on measures of social functioning and mental health.

Epidemiology

Prevalence estimates place the number of people with PBA between 1.5 and 2 million in the United States alone, which would be less than 1% of the US population even at the high end of the estimate. Some argue that the number is probably higher and that clinicians underdiagnose PBA. However, the prevalence estimate of 2 million is based on an online survey. Self-selected computer-savvy patients in at-risk groups evaluated their own symptoms and submitted their self-diagnoses. No doctor or clinic confirmed the data. Motivation to participate could have been influenced by the presence of symptoms, which would have skewed the results. The actual prevalence could very well be quite a bit lower than estimated.

Brief History

The Expression of the Emotions in Man and Animals by Charles Darwin was published in 1872. In Chapter VI, “Special Expressions of Man: Suffering and Weeping”, Darwin discusses cultural variations in the acceptability of weeping and the wide differences in individual responses to suffering. The chapter contains the following sentence:

We must not, however, lay too much stress on the copious shedding of tears by the insane, as being due to the lack of all restraint; for certain brain-diseases, as hemiplegia, brain-wasting, and senile decay, have a special tendency to induce weeping.

Terminology

Historically, there have been a variety of terms used for the disorder, including pseudobulbar affect, pathological laughter and crying, emotional lability, emotionalism, emotional dysregulation, or more recently, involuntary emotional expression disorder. The term pseudobulbar (pseudo- + bulbar) came from the idea that the symptoms seemed similar to those caused by a bulbar lesion (that is, a lesion in the medulla oblongata).

Terms such as forced crying, involuntary crying, pathological emotionality, and emotional incontinence have also been used, although less frequently.

In Popular Culture

Arthur Fleck, the central character of the 2019 film Joker, displays signs of pseudobulbar affect, which are said to be what Joaquin Phoenix used as inspiration for his character’s signature laugh.

In the 2019 movie Parasite, the character Ki-woo sustains head trauma, and although it is not clearly mentioned that he’s affected by pseudobulbar affect, he mentions not being able to stop laughing when thinking about all the events that occur in the movie.

In the 2020 movie Naan Sirithal, the character Gandhi (Hiphop Tamizha Adhi) suffers from pseudobulbar affect due to all the stress he suffers from various parts of his life gets accumulated and starts to laugh uncontrollably.

In the medical television show House, season 7, episode 8 (“Small Sacrifices”), the character Ramon Silva, played by Kuno Becker displays pseudobulbar affect, with uncontrollable incongruent laughter, while having the Marburg variety of multiple sclerosis.

In season 3, episode 9 of The Good Fight, the character Brenda DeCarlo, an external auditor, displays pseudobulbar affect, with uncontrollable incongruent laughter.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Pseudobulbar_affect >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is Neuroprotection?

Published on by Andrew Marshall1 Comment

Introduction

Neuroprotection refers to the relative preservation of neuronal structure and/or function.

In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation. It is a widely explored treatment option for many central nervous system (CNS) disorders including neurodegenerative diseases, stroke, traumatic brain injury, spinal cord injury, and acute management of neurotoxin consumption (i.e. methamphetamine overdoses). Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons.

Despite differences in symptoms or injuries associated with CNS disorders, many of the mechanisms behind neurodegeneration are the same. Common mechanisms of neuronal injury include decreased delivery of oxygen and glucose to the brain, energy failure, increased levels in oxidative stress, mitochondrial dysfunction, excitotoxicity, inflammatory changes, iron accumulation, and protein aggregation. Of these mechanisms, neuroprotective treatments often target oxidative stress and excitotoxicity—both of which are highly associated with CNS disorders. Not only can oxidative stress and excitotoxicity trigger neuron cell death but when combined they have synergistic effects that cause even more degradation than on their own. Thus limiting excitotoxicity and oxidative stress is a very important aspect of neuroprotection.

Common neuroprotective treatments are glutamate antagonists and antioxidants, which aim to limit excitotoxicity and oxidative stress respectively.

Excitotoxicity

Glutamate excitotoxicity is one of the most important mechanisms known to trigger cell death in CNS disorders. Over-excitation of glutamate receptors, specifically NMDA receptors, allows for an increase in calcium ion (Ca2+) influx due to the lack of specificity in the ion channel opened upon glutamate binding. As Ca2+ accumulates in the neuron, the buffering levels of mitochondrial Ca2+ sequestration are exceeded, which has major consequences for the neuron. Because Ca2+ is a secondary messenger and regulates a large number of downstream processes, accumulation of Ca2+ causes improper regulation of these processes, eventually leading to cell death. Ca2+ is also thought to trigger neuroinflammation, a key component in all CNS disorders.

Glutamate Antagonists

Glutamate antagonists are the primary treatment used to prevent or help control excitotoxicity in CNS disorders. The goal of these antagonists is to inhibit the binding of glutamate to NMDA receptors such that accumulation of Ca2+ and therefore excitotoxicity can be avoided. Use of glutamate antagonists presents a huge obstacle in that the treatment must overcome selectivity such that binding is only inhibited when excitotoxicity is present. A number of glutamate antagonists have been explored as options in CNS disorders, but many are found to lack efficacy or have intolerable side effects. Glutamate antagonists are a hot topic of research. Below are some of the treatments that have promising results for the future:

  • Estrogen: 17β-Estradiol helps regulate excitotoxicity by inhibiting NMDA receptors as well as other glutamate receptors.
  • Ginsenoside Rd: Results from the study show ginsenoside rd attenuates glutamate excitotoxicity. Importantly, clinical trials for the drug in patients with ischemic stroke show it to be effective as well as noninvasive.
  • Progesterone: Administration of progesterone is well known to aid in the prevention of secondary injuries in patients with traumatic brain injury and stroke.
  • Simvastatin: Administration in models of Parkinson’s disease have been shown to have pronounced neuroprotective effects including anti-inflammatory effects due to NMDA receptor modulation.
  • Memantine: As a low-affinity NMDA antagonist that is uncompetitive, memantine inhibits NMDA induced excitotoxicity while still preserving a degree of NMDA signalling.
  • Riluzole is an antiglutamatergic drug used to slow the progression of amyotrophic lateral sclerosis.

Oxidative Stress

Increased levels of oxidative stress can be caused in part by neuroinflammation, which is a highly recognised part of cerebral ischemia as well as many neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. The increased levels of oxidative stress are widely targeted in neuroprotective treatments because of their role in causing neuron apoptosis. Oxidative stress can directly cause neuron cell death or it can trigger a cascade of events that leads to protein misfolding, proteasomal malfunction, mitochondrial dysfunction, or glial cell activation. If one of these events is triggered, further neurodegradation is caused as each of these events causes neuron cell apoptosis. By decreasing oxidative stress through neuroprotective treatments, further neurodegradation can be inhibited.

Antioxidants

Antioxidants are the primary treatment used to control oxidative stress levels. Antioxidants work to eliminate reactive oxygen species, which are the prime cause of neurodegradation. The effectiveness of antioxidants in preventing further neurodegradation is not only disease dependent but can also depend on gender, ethnicity, and age. Listed below are common antioxidants shown to be effective in reducing oxidative stress in at least one neurodegenerative disease:

  • Acetylcysteine: It targets a diverse array of factors germane to the pathophysiology of multiple neuropsychiatric disorders including glutamatergic transmission, the antioxidant glutathione, neurotrophins, apoptosis, mitochondrial function, and inflammatory pathways.
  • Crocin: Derived from saffron, crocin has been shown to be a potent neuronal antioxidant.
  • Oestrogen: 17α-oestradiol and 17β-oestradiol have been shown to be effective as antioxidants. The potential for these drugs is enormous. 17α-oestradiol is the non-oestrogenic stereoisomer of 17β-oestradiol. The effectiveness of 17α-oestradiol is important because it shows that the mechanism is dependent on the presence of the specific hydroxyl group, but independent of the activation of oestrogen receptors. This means more antioxidants can be developed with bulky side chains so that they do not bind to the receptor but still possess the antioxidant properties.
  • Fish oil: This contains n-3 polyunsaturated fatty acids that are known to offset oxidative stress and mitochondrial dysfunction. It has high potential for being neuroprotective and many studies are being done looking at the effects in neurodegenerative diseases.
  • Minocycline: Minocycline is a semi-synthetic tetracycline compound that is capable of crossing the blood brain barrier. It is known to be a strong antioxidant and has broad anti-inflammatory properties. Minocyline has been shown to have neuroprotective activity in the CNS for Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, and ALS.
  • PQQ: Pyrroloquinoline quinone (PQQ) as an antioxidant has multiple modes of neuroprotection.
  • Resveratrol: Resveratrol prevents oxidative stress by attenuating hydrogen peroxide-induced cytotoxicity and intracellular accumulation of ROS. It has been shown to exert protective effects in multiple neurological disorders including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and ALS as well as in cerebral ischemia.
  • Vinpocetine: Vinpocetine exerts neuroprotective effects in ischaemia of the brain through actions on cation channels, glutamate receptors and other pathways. The drop in dopamine produced by vinpocetine may contribute to its protective action from oxidative damage, particularly in dopamine-rich structures. Vinpocetine as a unique anti-inflammatory agent may be beneficial for the treatment of neuroinflammatory diseases. It increases cerebral blood flow and oxygenation.
  • THC: Delta 9-tetrahydrocannabinol exerts neuroprotective and antioxidative effects by inhibiting NMDA neurotoxicity in neuronal cultures exposed to toxic levels of the neurotransmitter, glutamate.
  • Vitamin E: Vitamin E has had varying responses as an antioxidant depending on the neurodegenerative disease that it is being treated. It is most effective in Alzheimer’s disease and has been shown to have questionable neuroprotection effects when treating ALS. A meta-analysis involving 135,967 participants showed there is a significant relationship between vitamin E dosage and all-cause mortality, with dosages equal to or greater than 400 IU per day showing an increase in all-cause mortality. However, there is a decrease in all-cause mortality at lower doses, optimum being 150 IU per day. Vitamin E is ineffective for neuroprotection in Parkinson’s disease.

Stimulants

NMDA receptor stimulants can lead to glutamate and calcium excitotoxicity and neuroinflammation. Some other stimulants, in appropriate doses, can however be neuroprotective.

  • Selegiline: It has been shown to slow early progression of Parkinson’s disease and delayed the emergence of disability by an average of nine months.
  • Nicotine: It has been shown to delay the onset of Parkinson’s disease in studies involving monkeys and humans.
  • Caffeine: It is protective against Parkinson’s disease. Caffeine induces neuronal glutathione synthesis by promoting cysteine uptake, leading to neuroprotection.

Neuroprotectants (Cerebroprotectants) for Acute Ischemic Stroke

When applied to protecting the brain from the effects of acute ischemic stroke, neuroprotectants are often called cerebroprotectants. Over 150 drugs have been tested in clinical trials, leading to the regulatory approval of tissue plasminogen activator in several countries, the and approval of edaravone in Japan.

Other Neuroprotective Treatments

More neuroprotective treatment options exist that target different mechanisms of neurodegradation. Continued research is being done in an effort to find any method effective in preventing the onset or progression of neurodegenerative diseases or secondary injuries. These include:

  • Caspase inhibitors: These are primarily used and studied for their anti apoptotic effects.
  • Trophic factors: The use of trophic factors for neuroprotection in CNS disorders is being explored, specifically in ALS. Potentially neuroprotective trophic factors include CNTF, IGF-1, VEGF, and BDNF.
  • Therapeutic hypothermia: This is being explored as a neuroprotection treatment option for patients with traumatic brain injury and is suspected to help reduce intracranial pressure.
  • Erythropoietin has been reported to protect nerve cells from hypoxia-induced glutamate toxicity (see erythropoietin in neuroprotection).
  • Lithium exerts neuroprotective effects and stimulates neurogenesis via multiple signaling pathways; it inhibits glycogen synthase kinase-3 (GSK-3), upregulates neurotrophins and growth factors (e.g., brain-derived neurotrophic factor (BDNF)), modulates inflammatory molecules, upregulates neuroprotective factors (e.g., B-cell lymphoma-2 (Bcl-2), heat shock protein 70 (HSP-70)), and concomitantly downregulates pro-apoptotic factors. Lithium has been shown to reduce neuronal death, microglial activation, cyclooxygenase-2 induction, amyloid-β (Aβ), and hyperphosphorylated tau levels, to preserve blood-brain barrier integrity, to mitigate neurological deficits and psychiatric disturbance, and to improve learning and memory outcome.
  • Neuroprotection D1 and other neuroprotections and certain resolvins of the D series (i.e. RvD1, RvD2, RvD3, RvD4, RvD5, and RvD6) are docosanoid metabolites of the omega 3 fatty acid, docosahexaenoic acid (DHA) while resolvins of the E series (RvD1, RvD2, and RvD3) are eicosanoid metabolites of the omega 3 fatty acid, eicosapentaenoic acid (EPA). These metabolites, which are made by the action of cellular lipoxygenase, cyclooxygenase, and/or cytochrome P450 enzymes on DHA or EPA, have been shown to have potent anti-inflammation activity and to be neuroprotective in various models of inflammation-involving neurological diseases such as various degenerative diseases including Alzheimer’s disease. A metabolically resistant analogue of RvE1 is in development for the treatment of retinal disease and neuroprotection D1 mimetics are in development for treatment of neurodegenerative diseases and hearing loss.

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What is Logorrhoea?

Published on by Andrew Marshall1 Comment

Introduction

In psychology, logorrhea or logorrhoea (from Ancient Greek λόγος logos “word” and ῥέω rheo “to flow”), is a communication disorder that causes excessive wordiness and repetitiveness, which can cause incoherency.

Logorrhoea is sometimes classified as a mental illness, though it is more commonly classified as a symptom of mental illness or brain injury. This ailment is often reported as a symptom of Wernicke’s aphasia, where damage to the language processing centre of the brain creates difficulty in self-centred speech.

Refer to Tangential Speech.

Characteristics

Logorrhoea is characterised by the constant need to talk. Occasionally, patients suffering from logorrhoea may produce speech with normal prosody and a slightly fast speech rate. Other related symptoms include the use of neologisms (new words without clear derivation, e.g. hipidomateous for hippopotamus), words that bear no apparent meaning, and, in some extreme cases, the creation of new words and morphosyntactic constructions. From the “stream of unchecked nonsense often under pressure and the lack of self-correction” that the patient may exhibit, and their circumlocution (the ability to talk around missing words) we may conclude that they are unaware of the grammatical errors they are making.

Examples of Logorrhoea

When a clinician said, “Tell me what you do with a comb”, to a patient suffering from mild Wernicke’s aphasia (which produces the symptom of logorrhoea), the patient responded:

“What do I do with a comb … what I do with a comb. Well a comb is a utensil or some such thing that can be used for arranging and rearranging the hair on the head both by men and by women. One could also make music with it by putting a piece of paper behind and blowing through it. Sometimes it could be used in art – in sculpture, for example, to make a series of lines in soft clay. It’s usually made of plastic and usually black, although it comes in other colors. It is carried in the pocket or until it’s needed, when it is taken out and used, then put back in the pocket. Is that what you had in mind?”

In this case, the patient maintained proper grammar and did not exhibit any signs of neologisms. However, the patient did use an overabundance of speech in responding to the clinician, as most people would simply respond, “I use a comb to comb my hair.”

In a more extreme version of logorrhoea aphasia, a clinician asked a male patient, also with Wernicke’s aphasia, what brought him to the hospital. The patient responded:

“Is this some of the work that we work as we did before? … All right … From when wine [why] I’m here. What’s wrong with me because I … was myself until the taenz took something about the time between me and my regular time in that time and they took the time in that time here and that’s when the time took around here and saw me around in it’s started with me no time and I bekan [began] work of nothing else that’s the way the doctor find me that way…”

In this example, the patient’s aphasia was much more severe. Not only was this a case of logorrhoea, but this included neologisms (such as “taenz” for “stroke” and “regular time” for “regular bath”) and a loss of proper sentence structure.

Causes

Logorrhoea has been shown to be associated with traumatic brain injuries in the frontal lobe[7] as well as with lesions in the thalamus] and the ascending reticular inhibitory system and has been associated with aphasia. Logorrhoea can also result from a variety of psychiatric and neurological disorders including tachypsychia, mania, hyperactivity, catatonia, ADHD and schizophrenia.

Aphasias

Wernicke’s Aphasia, amongst other aphasias, are often associated with logorrhoea. Aphasia refers to the neurological disruption of language that occurs as a consequence of brain dysfunction. For a patient to truly have an aphasia, they cannot have been diagnosed with any other medical condition that may affect their cognition. Logorrhoea is a common symptom of Wernicke’s Aphasia, along with circumlocution, paraphasias, and neologisms. Often a patient with aphasia may present all of these symptoms at one time.

Treatment

Excessive talking may be a symptom of an underlying illness and should be addressed by a medical provider if combined with hyperactivity or symptoms of mental illness, such as hallucinations. Treatment of logorrhoea depends on its underlying disorder, if any. Antipsychotics are often used, and lithium is a common supplement given to manic patients. For patients with lesions of the brain, attempting to correct their errors may upset and anger the patients, since the language centre of their brain may not be able to process that what they are saying is incorrect and wordy.

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What is the Social Impact of Health Insurance Care Utilisation in Low- & Middle-Income Countries?

Published on by Andrew Marshall1 Comment

Research Paper Title

The impact of social, national and community-based health insurance on health care utilisation for mental, neurological and substance-use disorders in low- and middle-income countries: a systematic review.

Background

Whilst several systematic reviews conducted in Low- and Middle-Income Countries (LMICs) have revealed that coverage under social (SHI), national (NHI) and community-based (CBHI) health insurance has led to increased utilisation of health care services, it remains unknown whether, and what aspects of, these shifts in financing result in improvements to mental health care utilisation.

The main aim of this review was to examine the impact of SHI, NHI and CBHI enrolment on mental health care utilisation in LMICs.

Methods

Systematic searches were performed in nine databases of peer-reviewed journal articles: Pubmed, Scopus, SciELO via Web of Science, Africa Wide, CINAHL, PsychInfo, Academic Search Premier, Health Source Nursing Academic and EconLit for studies published before October 2018.

The quality of the studies was assessed using the Effective Public Health Practice Project quality assessment tool for quantitative studies.

Results

Eighteen studies were included in the review.

Despite some heterogeneity across countries, the results demonstrated that enrollment in SHI, CBHI and NHI schemes increased utilisation of mental health care.

This was consistent for the length of inpatient admissions, number of hospitalisations, outpatient use of rehabilitation services, having ever received treatment for diagnosed schizophrenia and depression, compliance with drug therapies and the prescriptions of more favourable medications and therapies, when compared to the uninsured.

The majority of included studies did not describe the insurance schemes and their organizational details at length, with limited discussion of the links between these features and the outcomes.

Given the complexity of mental health service utilisation in these diverse contexts, it was difficult to draw overall judgements on whether the impact of insurance enrollment was positive or negative for mental health care outcomes.

Conclusions

Studies that explore the impact of SHI, NHI and CBHI enrolment on mental health care utilisation are limited both in number and scope.

Despite the fact that many LMICs have been hailed for financing reforms towards universal health coverage, evidence on the positive impact of the reforms on mental health care utilisation is only available for a small sub-set of these countries.

Reference

Docrat, S., Besada, D., Cleary, S. & Lund, C. (2020) The impact of social, national and community-based health insurance on health care utilization for mental, neurological and substance-use disorders in low- and middle-income countries: a systematic review. Health Economics Review. 10(1), pp.11. doi: 10.1186/s13561-020-00268-x.