Abnormal movements known as athetoid movements are commonly associated with issues in the basal ganglia.

Cerebellar Dysfunction: Symptoms and Signs

Cerebellar dysfunction is a condition that affects the cerebellum, a part of the brain responsible for coordinating movement and balance. The symptoms and signs of cerebellar dysfunction include ataxia, intention tremor, nystagmus, broad-based gait, slurred speech, dysdiadochokinesis, and dysmetria (lack of finger-nose coordination).

Ataxia refers to the lack of coordination of voluntary movements, resulting in unsteady gait, difficulty with balance, and clumsiness. Intention tremor is a type of tremor that occurs during voluntary movements, such as reaching for an object. Nystagmus is an involuntary movement of the eyes, characterized by rapid, jerky movements.

Broad-based gait refers to a wide stance while walking, which is often seen in individuals with cerebellar dysfunction. Slurred speech, also known as dysarthria, is a common symptom of cerebellar dysfunction, which affects the ability to articulate words clearly. Dysdiadochokinesis is the inability to perform rapid alternating movements, such as tapping the fingers on the palm of the hand.

Dysmetria refers to the inability to accurately judge the distance and direction of movements, resulting in errors in reaching for objects of touching the nose with the finger. These symptoms and signs of cerebellar dysfunction can be caused by a variety of conditions, including stroke, multiple sclerosis, and alcoholism. Treatment depends on the underlying cause and may include medications, physical therapy, and surgery.

Overview of Cranial Nerves and Their Functions

The cranial nerves are a complex system of nerves that originate from the brain and control various functions of the head and neck. There are twelve cranial nerves, each with a specific function and origin. The following table provides a simplified overview of the cranial nerves, including their origin, skull exit, modality, and functions.

The first cranial nerve, the olfactory nerve, originates from the telencephalon and exits through the cribriform plate. It is a sensory nerve that controls the sense of smell. The second cranial nerve, the optic nerve, originates from the diencephalon and exits through the optic foramen. It is a sensory nerve that controls vision.

The third cranial nerve, the oculomotor nerve, originates from the midbrain and exits through the superior orbital fissure. It is a motor nerve that controls eye movement, pupillary constriction, and lens accommodation. The fourth cranial nerve, the trochlear nerve, also originates from the midbrain and exits through the superior orbital fissure. It is a motor nerve that controls eye movement.

The fifth cranial nerve, the trigeminal nerve, originates from the pons and exits through different foramina depending on the division. It is a mixed nerve that controls chewing and sensation of the anterior 2/3 of the scalp. It also tenses the tympanic membrane to dampen loud noises.

The sixth cranial nerve, the abducens nerve, originates from the pons and exits through the superior orbital fissure. It is a motor nerve that controls eye movement. The seventh cranial nerve, the facial nerve, also originates from the pons and exits through the internal auditory canal. It is a mixed nerve that controls facial expression, taste of the anterior 2/3 of the tongue, and tension on the stapes to dampen loud noises.

The eighth cranial nerve, the vestibulocochlear nerve, originates from the pons and exits through the internal auditory canal. It is a sensory nerve that controls hearing. The ninth cranial nerve, the glossopharyngeal nerve, originates from the medulla and exits through the jugular foramen. It is a mixed nerve that controls taste of the posterior 1/3 of the tongue, elevation of the larynx and pharynx, and swallowing.

The tenth cranial nerve, the vagus nerve, also originates from the medulla and exits through the jugular foramen. It is a mixed nerve that controls swallowing, voice production, and parasympathetic supply to nearly all thoracic and abdominal viscera. The eleventh cranial nerve, the accessory nerve, originates from the medulla and exits through the jugular foramen. It is a motor nerve that controls shoulder shrugging and head turning.

The twelfth cranial nerve, the hypoglossal nerve, originates from the medulla and exits through the hypoglossal canal. It is a motor nerve that controls tongue movement. Overall, the cranial nerves play a crucial role in controlling various functions of the head and neck, and any damage of dysfunction can have significant consequences.

Serotonin: Synthesis and Breakdown

Serotonin, also known as 5-Hydroxytryptamine (5-HT), is synthesized in the central nervous system (CNS) in the raphe nuclei located in the brainstem, as well as in the gastrointestinal (GI) tract in enterochromaffin cells. The amino acid L-tryptophan, obtained from the diet, is used to synthesize serotonin. L-tryptophan can cross the blood-brain barrier, but serotonin cannot.

The transformation of L-tryptophan into serotonin involves two steps. First, hydroxylation to 5-hydroxytryptophan is catalyzed by tryptophan hydroxylase. Second, decarboxylation of 5-hydroxytryptophan to serotonin (5-hydroxytryptamine) is catalyzed by L-aromatic amino acid decarboxylase.

Serotonin is taken up from the synapse by a monoamine transporter (SERT). Substances that block this transporter include MDMA, amphetamine, cocaine, TCAs, and SSRIs. Serotonin is broken down by monoamine oxidase (MAO) and then by aldehyde dehydrogenase to 5-Hydroxyindoleacetic acid (5-HIAA).

When there is a blockage in the anterior cerebral artery, the legs are typically impacted more than the arms. Additionally, a common symptom is abulia, which is a lack of determination of difficulty making firm decisions.

Brain Blood Supply and Consequences of Occlusion

The brain receives blood supply from the internal carotid and vertebral arteries, which form the circle of Willis. The circle of Willis acts as a shunt system in case of vessel damage. The three main vessels arising from the circle are the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA). Occlusion of these vessels can result in various neurological deficits. ACA occlusion may cause hemiparesis of the contralateral foot and leg, sensory loss, and frontal signs. MCA occlusion is the most common and can lead to hemiparesis, dysphasia/aphasia, neglect, and visual field defects. PCA occlusion may cause alexia, loss of sensation, hemianopia, prosopagnosia, and cranial nerve defects. It is important to recognize these consequences to provide appropriate treatment.

The Use of Star Charts in Behavioral Management

Star charts have proven to be effective in managing enuresis, encopresis, and acute phase despondency. In cases of encopresis, the star chart reward system has been successful in about 20 to 30% of cases. The use of a wall chart to graphically depict the time spent off the ventilator each day has also been effective in patients with severe ventilator impairments.

The reward system in the form of a star chart is a type of positive reinforcement, where behavior is strengthened by the presentation of something pleasant. This is a form of operant conditioning, where the animal is active and learns through action. In contrast, classical conditioning involves passive of restrained animals and the use of conditioned and unconditioned stimuli.

Social learning theories rely on role modeling, identification, and human interactions. While social learning combines classical and operant conditioning, observation of models may be a major factor in the learning process. Higher order conditioning is another form of classical conditioning, where a conditioned stimulus is paired with another stimulus to produce a further conditioned response.

Culture bound illnesses are psychiatric conditions that are specific to one particular culture. There are many different types of culture bound illnesses, including Amok, Shenjing shuairuo, Ataque de nervios, Bilis, colera, Bouffee delirante, Brain fag, Dhat, Falling-out, blacking out, Ghost sickness, Hwa-byung, wool-hwa-byung, Koro, Latah, Locura, Mal de ojo, Nervios, Rootwork, Pibloktoq, Qi-gong psychotic reaction, Sangue dormido, Shen-k’uei, shenkui, Shin-byung, Taijin kyofusho, Spell, Susto, Zar, and Wendigo.

Some of the most commonly discussed culture bound illnesses include Amok, which is confined to males in the Philippines and Malaysia who experience blind, murderous violence after a real of imagined insult. Ataque de nervios is a condition that occurs in those of Latino descent and is characterized by intense emotional upset, shouting uncontrollably, aggression, dissociation, seizure-like episodes, and suicidal gestures. Brain fag is a form of psychological distress first identified in Nigerian students in the 1960s but reported more generally in the African diaspora. It consists of a variety of cognitive and sensory disturbances that occur during periods of intense intellectual activity. Koro is a condition that affects Chinese patients who believe that their penis is withdrawing inside their abdomen, resulting in panic and the belief that they will die. Taijin kyofusho is a Japanese culture bound illness characterized by anxiety about and avoidance of interpersonal situations due to the thought, feeling, of conviction that one’s appearance and actions in social interactions are inadequate of offensive to others. Finally, Wendigo is a culture bound illness that occurs in Native American tribes during severe winters and scarcity of food, characterized by a distaste for food that leads to anxiety and the belief that one is turning into a cannibalistic ice spirit.

Huntington’s Disease: Genetics and Pathology

Huntington’s disease is a genetic disorder that follows an autosomal dominant pattern of inheritance. It is caused by a mutation in the Huntington gene, which is located on chromosome 4. The mutation involves an abnormal expansion of a trinucleotide repeat sequence (CAG), which leads to the production of a toxic protein that damages brain cells.

The severity of the disease and the age of onset are related to the number of CAG repeats. Normally, the CAG sequence is repeated less than 27 times, but in Huntington’s disease, it is repeated many more times. The disease shows anticipation, meaning that it tends to worsen with each successive generation.

The symptoms of Huntington’s disease typically begin in the third of fourth decade of life, but in rare cases, they can appear in childhood of adolescence. The most common symptoms include involuntary movements (chorea), cognitive decline, and psychiatric disturbances.

The pathological hallmark of Huntington’s disease is the gross bilateral atrophy of the head of the caudate and putamen, which are regions of the brain involved in movement control. The EEG of patients with Huntington’s disease shows a flattened trace, indicating a loss of brain activity.

Macroscopic pathological findings include frontal atrophy, marked atrophy of the caudate and putamen, and enlarged ventricles. Microscopic findings include neuronal loss and gliosis in the cortex, neuronal loss in the striatum, and the presence of inclusion bodies in the neurons of the cortex and striatum.

In conclusion, Huntington’s disease is a devastating genetic disorder that affects the brain and causes a range of motor, cognitive, and psychiatric symptoms. The disease is caused by a mutation in the Huntington gene, which leads to the production of a toxic protein that damages brain cells. The pathological changes in the brain include atrophy of the caudate and putamen, neuronal loss, and the presence of inclusion bodies.

Phenethylamine is NOT a metabolite of MAO-A, but rather of MAO-B.

Monoamine Oxidase (MAO)

Monoamine oxidase (MAO) is an enzyme that plays a crucial role in the metabolism of various neurotransmitters and hormones in the body. There are two forms of MAO, namely MAO-A and MAO-B. MAO-A is responsible for metabolising dopamine, serotonin, noradrenaline, adrenaline, and melatonin, while MAO-B metabolises dopamine and phenylethylamine. These neurotransmitters and hormones are essential for regulating mood, emotions, and behaviour. Any imbalance in their levels can lead to various mental health disorders such as depression, anxiety, and bipolar disorder. Therefore, MAO inhibitors are commonly used as antidepressants and anxiolytics to regulate the levels of these neurotransmitters and hormones in the body.

Echolalia refers to the act of repeating someone else’s spoken words without any meaningful connection of context. This behavior is often observed in individuals with certain neurological of developmental disorders.

Formal Thought Disorders

In formal thought disorders, changes in the speed, coherence, and cogency of thought can be observed from a patient’s speech. These disorders can also be self-reported and may be accompanied by enhanced use of nonverbal language. One possible indication is a lack of an adequate connection between two consecutive thoughts, which is called ‘asyndesis’.

There are several types of formal thought disorders, including inhibited thinking, retarded thinking, circumstantial thinking, restricted thinking, perseverative thinking, rumination, pressured thinking, flight of ideas, tangential thinking, thought blocking, disruption of thought, incoherence/derailment, and neologisms.

Inhibited thinking is about the subjective experience of the patient, who may feel that their thinking process is slowed down of blocked by an inner wall of resistance. Retarded thinking, on the other hand, is about the observed quality of thought as inferred through speech, where the flow of thought processes is slowed down and sluggish.

Circumstantial thinking refers to an inability to separate the essential from the unessential during a conversation without rendering the conversation incoherent. Restricted thinking involves a limited range of thought content, fixation on one particular topic of a small number of topics only, and a stereotyped pattern of thinking.

Perseverative thinking is characterized by the persistent repetition of previously used words, phrases, of details to the point where they become meaningless in the context of the current stage of the interview. Rumination is the endless mental preoccupation with, of excessive concern over, mostly unpleasant thoughts.

Pressured thinking, also known as crowding of thought, is when the patient feels helplessly exposed to the pressures of floods of different ideas of thoughts. Flight of ideas involves an increasing multitude of thoughts and ideas which are no longer firmly guided by clear goal-directed thinking.

Tangential thinking occurs when the patient appears to understand the contents of the questions addressed to them but provides answers which are completely out of context. Thought blocking of disruption of thought refers to sudden disruption of an otherwise normal flow of thought of speech for no obvious reason.

Incoherence of derailment is when the interviewer is unable to establish sensible connections between the patient’s thinking and verbal output, which is sometimes also called derailment. Neologisms involve the formation of new words of usage of words which disregard normal conventions and are generally not easily understandable.

Many people confuse zero and first order kinetics, but it’s important to remember that zero order is non-linear while first order is linear. The linearity of first order kinetics refers to proportionality. The graphs used to illustrate this concept can be misleading, so it’s crucial to have a clear understanding of the difference between the two.

The half-life of a drug is the time taken for its concentration to fall to one half of its value. Drugs with long half-lives may require a loading dose to achieve therapeutic plasma concentrations rapidly. It takes about 4.5 half-lives to reach steady state plasma levels. Most drugs follow first order kinetics, where a constant fraction of the drug in the body is eliminated per unit time. However, some drugs may follow zero order kinetics, where the plasma concentration of the drug decreases at a constant rate, despite the concentration of the drug. For drugs with nonlinear kinetics of dose-dependent kinetics, the relationship between the AUC of CSS and dose is not linear, and the kinetic parameters may vary depending on the administered dose.

Types of Tremor

Essential Tremor

Otherwise known as benign essential tremor, this is the most common type of tremor. It is not associated with any underlying pathology. It usually begins in the 40’s, affects mainly the hands, and is slowly progressive. It tends to worsen with heightened emotion. It usually presents with unilateral upper limb involvement then progresses to both limbs.

Parkinsonian Tremor

This tremor is associated with Parkinson’s disease. It is classically described as ‘pill rolling’ due to the characteristic appearance of the fingers.

Cerebellar Tremor

Otherwise known as an intention tremor. This is a slow, coarse tremor which gets worse with purposeful movement. This is seen in lithium toxicity (note that the tremor seen as a side effect of long term lithium is fine and classed as physiological).

Psychogenic Tremor

Also known as a hysterical tremor. This type of tremor tends to appear and disappear suddenly and is hard to characterise due to its changeable nature. It tends to improve with distraction.

Physiologic Tremor

This is a very-low-amplitude fine tremor that is barely visible to the naked eye. It is present in every normal person while maintaining a posture of movement. It becomes enhanced and visible in many conditions such as anxiety, hyperthyroidism, alcohol withdrawal, and as drug induced side effects.

It is useful to have a basic idea about the frequencies of different types of tremor.

Type of Tremor Frequency

Intention 2-3Hz

Parkinsonian 5Hz

Essential 7Hz

Physiological 10Hz

Psychogenic variable

Mitgehen is a type of extreme cooperation that is observed in catatonia, where the patient moves their body in the direction of even the slightest pressure. It is crucial that the patient has been instructed to resist manipulation. This phenomenon is also referred to as the ‘angle poise lamp sign’ and is a form of automatic obedience. Catalepsy is another sign seen in catatonia, where patients maintain unusual postures for extended periods of time. In contrast, cataplexy is a sudden loss of muscle tone that leads to collapse and is commonly observed in narcolepsy. Gegenhalten is an involuntary resistance to passive movements. Mitmachen is a milder form of automatic obedience, where the patient’s body can be moved into any position without resistance when instructed to resist manipulation. Mitmachen is less severe than mitgehen, as the pressure required to elicit movements in mitgehen is very minimal.

Antipsychotic drugs such as chlorpromazine have an antidopaminergic effect, which can lead to hyperprolactinemia and hypogonadism. Additionally, they can cause a serious condition called neuroleptic malignant syndrome, which is characterized by hyperthermia, muscular rigidity, and altered consciousness. This syndrome is caused by the blocking of dopamine receptors and is more commonly associated with typical antipsychotics like chlorpromazine, haloperidol, and trifluoperazine. However, cases have also been reported with most atypical antipsychotic agents.

The Henderson hospital model exemplifies the four principles that underlie the therapeutic community, which include communalism, permissiveness, democratisation, and reality confrontation. These principles are reflected in the way staff and inmates interact, with a focus on mutual support and learning, tolerance of unpredictable behavior, shared decision-making, and open and honest communication about distortions from reality.

Aqueous humor is a clear protein free fluid secreted by the ciliary body, it travels to the anterior chamber through the pupil and is absorbed through a network of trabeculae into the canal of schlemm

The DSM-IV-TR uses a multi-axial system to diagnose mental disorders. Axis II covers developmental and personality disorders, such as autism and borderline personality disorder. Axis I covers clinical syndromes, like depression and schizophrenia. Axis III includes physical conditions that may contribute to mental illness, such as brain injury of HIV/AIDS. Axis IV rates the severity of psychosocial stressors, such as job loss of marriage, that may impact the person’s mental health. Finally, Axis V rates the person’s level of functioning, both currently and in the past year, to help the clinician understand how the other axes are affecting the person and what changes may be expected.

Individuals who are homozygous for APOE 4 have a risk of 10-30 times higher than those who do not have this genetic variant, while those who are heterozygous have a risk that is 3 times higher.

Genetics plays a role in the development of Alzheimer’s disease, with different genes being associated with early onset and late onset cases. Early onset Alzheimer’s, which is rare, is linked to three genes: amyloid precursor protein (APP), presenilin one (PSEN-1), and presenilin two (PSEN-2). The APP gene, located on chromosome 21, produces a protein that is a precursor to amyloid. The presenilins are enzymes that cleave APP to produce amyloid beta fragments, and alterations in the ratios of these fragments can lead to plaque formation. Late onset Alzheimer’s is associated with the apolipoprotein E (APOE) gene on chromosome 19, with the E4 variant increasing the risk of developing the disease. People with Down’s syndrome are also at high risk of developing Alzheimer’s due to inheriting an extra copy of the APP gene.

Understanding the Placebo Effect

In general, a placebo is an inert substance that has no pharmacological activity but looks, smells, and tastes like the active drug it is compared to. The placebo effect is the observable improvement seen when a patient takes a placebo, which results from patient-related factors such as expectations rather than the placebo itself. Negative effects due to patient-related factors are termed the nocebo effect.

Active placebos are treatments with chemical activity that mimic the side effects of the drug being tested in a clinical trial. They are used to prevent unblinding of the drug versus the placebo control group. Placebos need not always be pharmacological and can be procedural, such as sham electroconvulsive therapy.

The placebo effect is influenced by factors such as the perceived strength of the treatment, the status of the treating professional, and the branding of the compound. The placebo response is greater in mild illness, and the response rate is increasing over time. Placebo response is usually short-lived, and repeated use can lead to a diminished effect, known as placebo sag.

It is difficult to separate placebo effects from spontaneous remission, and patients who enter clinical trials generally do so when acutely unwell, making it challenging to show treatment effects. Breaking the blind may influence the outcome, and the expectancy effect may explain why active placebos are more effective than inert placebos. Overall, understanding the placebo effect is crucial in clinical trials and personalized medicine.

Non-Mendelian inheritance patterns include mitochondrial inheritance, trinucleotide expansion, mosaicism, and genomic imprinting. These patterns do not follow the typical Mendelian principles. Examples of non-Mendelian mitochondrial inheritance include Leber’s hereditary optic neuropathy and MELAS syndrome, which is characterized by mitochondrial myopathy, encephalopathy, lactic acidosis, and recurrent stroke.

On the other hand, Mendelian genetic inheritance patterns include autosomal dominant, autosomal recessive, and sex-linked disorders such as X-linked dominant and X-linked recessive.

Mitochondrial DNA abnormalities can lead to various diseases, including MELAS syndrome. Mitochondrial DNA is inherited solely from the mother’s ovum, and the embryo’s mitochondria are entirely maternally derived. Most mitochondrial diseases manifest as myopathies and neuropathies.

The movements observed in chorea are characterized as both jerky and flowing, often described as resembling a dance. It is important to distinguish chorea from athetosis, which is less abrupt and more akin to the movements of a worm. Sydenham’s chorea, which typically affects children following an infection with Group A beta-haemolytic Streptococcus, was historically known as St Vitus’ dance.

Movement Disorders: Key Features

Movement disorders refer to a range of conditions that affect voluntary muscle movements. These disorders can be caused by various factors, including neurological conditions, medication side effects, and metabolic imbalances. The following table outlines some of the key features of common movement disorders:

Akinesia: Absence of loss of control of voluntary muscle movements, often seen in severe Parkinson’s disease.

Bradykinesia: Slowness of voluntary movement, a core symptom of Parkinson’s disease.

Akathisia: Subjective feeling of inner restlessness, often caused by antipsychotic medication use.

Athetosis: Continuous stream of slow, flowing, writhing involuntary movements, often seen in cerebral palsy, stroke, and Huntington’s disease.

Chorea: Brief, quasi-purposeful, irregular contractions that appear to flow from one muscle to the next, often seen in Huntington’s disease and Wilson’s disease.

Dystonia: Involuntary sustained of intermittent muscle contractions that cause twisting and repetitive movements, abnormal postures, of both.

Dyskinesia: General term referring to problems with voluntary movements and the presence of involuntary movements, often drug-induced.

Myoclonus: A sequence of repeated, often non-rhythmic, brief shock-like jerks due to sudden involuntary contraction of relaxation of one of more muscles.

Parkinsonism: Syndrome characterized by tremor, rigidity, and bradykinesia.

Tic: Sudden, repetitive, non-rhythmic, stereotyped motor movement of vocalization involving discrete muscle groups, often seen in Tourette’s syndrome.

Tremor: Involuntary, rhythmic, alternating movement of one of more body parts, often seen in essential tremor, Parkinson’s disease, and alcohol withdrawal.

Hemiballismus: Repetitive, but constantly varying, large amplitude involuntary movements of the proximal parts of the limbs, often seen in stroke and traumatic brain injury.

Stereotypies: Repetitive, simple movements that can be voluntarily suppressed, often seen in autism and intellectual disability.

It is important to consider the underlying conditions and factors that may contribute to movement disorders in order to properly diagnose and treat these conditions.