CA LÂM SÀNG 18

Bupropion is an atypical antidepressant that acts as a dopamine and norepinephrine reuptake inhibitor. It is also indicated for smoking cessation.

Levominalcipran is a serotonin-norepinephrine reuptake inhibitor (SNRI). Should the patient fail a trial of a SSRI, augmentation or transition to an SNRI is an appropriate next step of management.

Mirtazapine is a tetracyclic antidepressant used to treat atypical depression by antagonizing presynaptic α2 adrenergic receptorsand postsynaptic serotonin 5-HT2 and serotonin 5-HT3 receptors. An atypical antidepressant is not a first-line treatment for depression.

Major takeaway
In the pharmacological management of major depressive disorder, a selective serotonin reuptake inhibitors such as sertraline and fluoxetine is the drug of choice.
Main explanation
The monoamine hypothesis of depression states that depression in a patient of the anxiousand obsessive-compulsive type, serotonin is likely the neurotransmitter of malfunction. As such, a selective serotonin reuptake inhibitor (SSRI) would be the drug of choice. This patient also displays symptoms of an anxiety disorder with his face picking and nail biting. Of the SSRI drug group, sertraline is reputedly one of the more anxiolytic SSRIs, and has a milder side effect profile and a low price due to the size of its market and the existence of generics.

Should the patient fail a trial of a SSRI, augmentation or transition to an SNRI (e.g. venlafaxineand levomilnacipran), or less preferably a tricyclic antidepressant, monoamine oxidase inhibitor, or atypical antidepressant (e.g. trazodone, mirtazapine, bupropion, and vortioxetine) could be attempted as symptoms and conditions warrant.

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI). Should the patient fail a trial of a SSRI, augmentation or transition to an SNRI is an appropriate next step of management.

Pseudomonas is associated with bacterial conjunctivitis and fulminant bacterial keratitis. Bacterial keratitis is most often caused by extended contact lens wear. It is characterized by foreign body sensation and trouble keeping the affected eye open.

S. aureus is a common cause of bacterial conjunctivitis. While viral conjunctivitis is associated with watery discharge, the discharge seen in bacterial conjunctivitis is often thick and mucopurulent.

S. epidermidis can also cause bacterial conjunctivitis. Bacterial conjunctivitis typically only affects one eye. The eye is often “stuck shut” in the morning.

Major takeaway
Viral conjunctivitis is characterized by rapid bilateral involvement, watery discharge, presence of tarsal follicles, and a tender pre-auricular lymph node. Adenovirus is a the most common cause of viral conjunctivitis.
Main explanation
Adenovirus is a common cause of viral conjunctivitis and is highly contagious. Classic symptoms include conjunctival injection with a watery discharge. Tearing rather than watery discharge may also be observed. Individuals with viral conjunctivitis may experience crusting in the morning but do not experience significant mucopurulent discharge throughout the day. The infection may begin in one eye but quickly spreads to the other eye within 24-48 hours. Mildly decreased vision and mild photophobia may also be present. Signs and symptoms that suggest viral conjunctivitis include a follicular (bumpy) appearance of the tarsal conjunctiva and a tender pre-auricular lymph node. Viral conjunctivitis is typically a self-limiting infection, and therapy is mostly supportive.

Mumps infection is characterized by bilateral viral conjunctivitis and parotitis. In the United States, mumps infections remains relatively rare compared to adenoviral conjunctivitis despite an elevated rate of measles-mumps-rubella vaccinationnoncompliance. Tender preauricular lymph nodes must be distinguished from tender parotid glands which would increase the suspicion for mumps.

Anorexia nervosa is an eating disorder with/without bulimia. Bulimia is defined as binge eating, with or without purging, while maintaining a normal body weight.

Anorexia nervosa could cause secondary amenorrhea because of low body weight and consequent hormonal disruption. There is usually no endocrine pathology to the amenorrhea.

Anorexia nervosa is an eating disorder that could lead to hormone imbalance, causing amenorrhea. In such cases, pregnancy testare usually negative.

Anorexia nervosa is an eating disorder that could lead to amenorrhea. Placing this patient on oral contraceptives does not address the issue of being underweight and malnourished.

Major takeaway
Anorexia nervosa (AN) is a potentially life-threatening eating disorder. Family therapy is usually the first means of management. If this is not applicable, cognitive behavioural therapy could be used.

Main explanation
Anorexia nervosa (AN) is a potentially life-threatening eating disorder characterized by the inability to maintain a minimally normal weight, a devastating fear of weight gain, relentless dietary habits that prevent weight gain, and a disturbance in the way in which body weightand shape are perceived. It could be associated with bulimic and non-bulimic episodes. It could lead to secondary amenorrhea in healthy females. Amenorrhea results from disorders in the hypothalamic-pituitary-ovarian axis in which levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are low despite low levels of estrogen. Due to this, reversion to the prepubertal state occurs, and the LH response to gonadotropin-releasing hormone (GnRH) is blunted. This blunted response is insufficient to maintain menstrual integrity, and amenorrhearesults. Management usually involve psychotherapy, namely cognitive behavioural therapy and/or nutritional rehabilitation. Misconceptions and misunderstandings about food and body image need to be addressed so that the patient can knowingly and willingly change for the better. Family therapy may also prove useful.

Major takeaway
Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, is the most common primary malignant brain tumor in adults. It is highly aggressive and the prognosis is usually less than a year. It will often “cross the midline” on imaging (butterfly glioma)

Main explanation
Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, is the most common primary malignant brain tumor in adults. It is highly aggressive and the prognosis is usually less than a year. It will often “cross the midline” on imaging (butterfly glioma). On histology, diagnosis can be aided by staining with glial fibrillary acidic protein, GFAP. The cells appear in a pseudopalisading pattern with areas of central hemorrhage and necrosis. Most “cancer headaches” are classically worse in the morning.

The patient is Gene Siskel, movie critic and half of the famous Siskel & Ebert duo. After complaining of severe headaches, Siskel was diagnosed with a malignant brain tumor and underwent surgery in May 1998. He returned to the Siskel and Ebert television show several months later, but in February he underwent a second surgical procedure and died in 1999

Meningiomas are benign brain tumors that arise from cells of the arachnoid mater and may present with seizures. They often occur along the parasagittal line and are attached to the dura. On histology, they typically show psammoma bodies.

This would be a much more acute onset and present with fevers, headache, nuchal rigidity. Begin empiric antibiotics and steroids(reduce intracerebral swelling/scarring complications). CT shows ventricular enlargement and sulcal effacement (from high intracerebral pressures)

Ingestion of Taenia solium (pork tapeworm) eggs in contaminated food or water can lead to brain cysts and headache, seizures, stroke, and neuropsychiatric dysfunction. CT shows multiple calcified cystic lesions. In the US this disease is mainly seen in immigrants. Treatment is albendazole plus corticosteroid.

Most often in obese females on oral contraceptive pills (OCPs); associated symptoms include vomiting and blurred vision. Head imaging is generally normal. Diagnosis via lumbar puncture opening pressure and treatment is cerebrospinal fluid removal and discontinuation OCPs.

Major takeaway
Amyotrophic lateral sclerosis (ALS or Lou Gehrig disease) is a disorder that involves the death of neurons that control voluntary muscles. ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size. This results in difficulty speaking, swallowing, and breathing.

Main explanation
Amyotrophic lateral sclerosis (ALS or Lou Gehrig disease) is a disorder that involves the death of neurons that control voluntary muscles. The cause is not known in 90%-95% of cases and about 5–10% of cases are inherited from a person’s parents. A defect on chromosome 21, which codes for superoxide dismutase 1 (SOD1), is associated with about 20% of familial cases of ALS, or about 2% of ALS cases overall. Diagnosis is made with clinical reference, with a nerve conduction study, and electromyography. ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size. This results in difficulty speaking, swallowing, and breathing. No cure for ALS is known but it is often treated with riluzole in attempts to slow the progression of disease. Riluzole works by decreasing presynaptic glutamate release, thereby limiting cytotoxic effects of this neurotransmitter. Non-invasive ventilation results in improved quality and length of life. ALS starts around the age of 60 and in inherited cases around the age of 50. The average survival from onset to death is 3 to 4 years. About 10% survive longer than 10 years and most die from respiratory failure.

Cervical radiculopathy is a dysfunction of a nerve root of the cervical spine. The hallmark of acute or chronic nerve root compression is pain. Pain due to nerve root compression follows a dermatomal distribution and is accompanied by paresthesia or sensory loss, and by loss of power in the muscles.

Guillain-Barré syndrome (GBS) is a demyelinating neuropathy with ascending weakness. The patient with GBS presents 2-4 weeks following a benign respiratory or gastrointestinal illness with complaints of finger dysesthesias and proximal muscle weakness of the lower extremities.

Hypertensive emergency is characterized by uncontrolled blood pressure that lead to progressive or impending end-organ dysfunction. Neurologic end-organ damage due to uncontrolled blood pressure include hypertensive encephalopathy, cerebral vascular accident/cerebral infarction, subarachnoid hemorrhage, and/or intracranial hemorrhage.

An acute vascular occlusion produces heterogeneous regions of ischemia in the affected vascular territory. Common signs of strokeinclude acute hemiparesis or hemiplegia, acute hemisensory loss, complete or partial hemianopia, monocular/binocular visual loss, dysarthria, ataxia, vertigo, and sudden decrease in consciousness.

Although teratogens may play a role in the development of deformities in a neonate, it is not as likely as intrauterine compression to cause unilateral clubfoot specifically.

Major takeaway
Clubfoot is a relatively common congenital deformity that is characterized by the inability to dorsiflex at the ankle. Although there can be multiple causes for clubfoot, unilateral cases are most likely caused by intrauterine compression.

Main explanation
Clubfoot, sometimes called talipes equinovarus, is a congenital deformity that affects up to 1 out of 1000 live births. It is characterized by one or both feet being extremely plantar-flexedwith inversion of the arch. Infants with this deformity characteristically are unable to dorsiflexat the ankle. Because this child’s presentation is unilateral, and because gentle manipulation can return the foot to a normal condition, the most likely etiology is a “packaging problem,” in which the foot happened to be held in that position in utero. Bilateral cases, or cases in which a normal position cannot be readily achieved, are more often associated with genetic abnormalities such as aneuploidy or other mutations.

Although the deformity may resolve after birth in some cases, the deformity in most cases is still and will require treatment. Left untreated, clubfoot can lead to severe painful deformities and can cause a child to end up walking on the outer aspects of their feet. Clubfoot is preferentially treated with the Ponseti method of casting and bracing. This management technique involves serial weekly cast changes to promote tendo achilles lengthening.

Clubfoot is a common birth defect that results in the appearance of internal rotation at the ankle, and is not associated with central nervous system defects.

Aneuploidy is the presence of an abnormal number of chromosomes. Although genetics may play a role in clubfoot, it is not generally associated with unilateral clubfoot.

Cerebral palsy is a result of abnormal brain development and is not generally associated as the causative agent of clubfoot.

Epidural hematoma is a condition that manifests after a cranioencephalic traumatism causes an intracranial arterial bleed, which in turn increases pressure in the brain. A lucid interval followed by loss of consciousness are the expected symptoms.

A myocardial infarction is characterized by signs of heart failure and retrosternal chest pain with radiation to the jaw, neck, and left arm.

Major takeaway
A stroke that affects Broca’s area is the most common cause of expressive aphasia. Atrial fibrillation raises suspicion of a thrombotic embolism to the brain.
Main explanation
The most common cause of expressive aphasia is stroke. Thrombosis or embolism cause ischemic stroke because of insufficient blood flow to the brain. When a patient’s symptomatology is characterized by acute aphasia and physical examination shows symptoms of atrial fibrillation (e.g. fatigue, shortness of breath, palpitations, confusion, dizziness and chest pain), embolism is suspected. The most appropriate first step in management is to perform a computerized tomography (CT) scan, without contrast material, to rule out an hemorrhagic stroke. Some form of aphasia occurs in 34-38% of stroke patients. In most cases, expressive aphasia is caused by a stroke in Broca’s area, which corresponds to the posterior part of the left inferior frontal gyrus.

A subdural hematoma is a condition that manifests after a cranioencephalic traumatism causes an intracranial bleeding of the bridging veins, which in turn increases pressure in the brain. The bleeding can occur either quickly, resulting in acute presentations, or slowly, resulting in symptoms over several days or weeks.

In head trauma, physical examination shows skull fracture (basilar skull fracture is characterized by “raccoon eyes”, Battle’s sign, hemotympanum, cerebrospinal fluid rhinorrhea and otorrhea), eye movement disorders, bruises on the scalp or face, or lacerations to the scalp and resulting hemorrhage of the skin.

Agoraphobia is a type of anxiety disorder in which you fear and often avoid places or situations that might cause you to panic and make you feel trapped, helpless or embarrassed.

Culture-bound syndrome, culture-specific syndrome or folk illness is a combination of psychiatric and somatic symptoms that are considered to be a recognizable disease only within a specific society or culture

Generalized anxiety disorder a psychological disorder characterized by excessive or disproportionate anxiety about several aspects of life, such as work, social relationships, or financial matters

Panic disorder is diagnosed in people who experience spontaneous seemingly out-of-the-blue panic attacks and are preoccupied with the fear of a recurring attack. Panic attacks occur unexpectedly, sometimes even during sleep

Major takeaway
Separation anxiety disorder (SAD) is a psychological condition in which an individual experiences excessive anxiety regarding separation from home or from people to whom the individual has a strong emotional attachment (e.g. a parent, caregiver, or siblings).
Main explanation
According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition(DSM-5), separation anxiety disorder is a fairly common anxiety disorder, occurring in youth younger than 18 years (persistent and lasting for at least 4 weeks) and in adults (typically requiring a duration of 6 mo or more). Separation anxiety disorder can also be associated with panic attacks that occur with comorbid panic disorder. Separation anxiety disorder consists of persistent and excessive anxiety beyond that expected for the child’s developmental level related to separation or impending separation from the attachment figure (eg, primary caretaker, close family member) as evidenced by at least 3 of the following criteria:
1. Recurrent excessive distress when anticipating or experiencing separation from home or from major attachment figures
2. Persistent and excessive worry about losing major attachment figures or about possible harm to them, such as illness, injury, disasters, or death
3. Persistent and excessive worry about experiencing an untoward event (eg, getting lost, being kidnapped, having an accident, becoming ill) that causes separation from a major attachment figure
4. Persistent reluctance or refusal to go out, away from home, to school, to work, or elsewhere because of fear of separation

Cytomegalovirus, or CMV, is another infectious cause of esophagitis that may occur in AIDS-patients with CD4 counts below 100. However, on endoscopy, it typically appears as linear ulcers instead of white plaques or plaques.

Like other pathologies that involve eosinophils, eosinophilic esophagitis is something that occurs in atopic patients. When allergens , e.g., food or stomach acid, interact with the esophageal mucosa, eosinophils release damaging compounds that lead to esophageal rings and symptoms of dysphagia that do not respond to gastroesophageal reflux disease therapy.

Major takeaway
Esophageal candidiasis is an infection, usually caused by Candida albicans, that typically occurs in patients who suffer from AIDS with CD4 counts below 100cells/microliter. The most common symptoms are odynophagia and dysphagia, and oropharyngeal thrush may or may not be currently present. Diagnosis can be confirmed by EGD with biopsy.
Main explanation
The majority of esophageal candidiasis cases, usually caused by Candida albicans, occur in immunocompromised patients, such as those who are taking steroids, undergoing chemotherapy, or who are HIV-positive with CD4 T-cell counts below 100cells/microliter. Though oropharyngeal candidiasis, also called thrush, is the most common opportunistic infection in HIV-positive people, it’s absence does not preclude the possibility that the infection is present within the esophagus. When the infection is just in the oropharynx, where it can be differentiated from leukoplakia by the ease with which it can be scraped off with a tongue blade (budding yeasts with pseudohyphae are seen on microscopic examination), and it can be treated with nonabsorbable topical antifungals such as nystatin (a liquid suspension that patients are taught to “swish and swallow”). However, as esophageal candidiasis is considered more invasive, it requires systemic antifungal treatment, typically with fluconazole for 14-21 days. When these patients present with dysphagia or odynophagia, they can be treated empirically with an antifungal, but an esophagogastroduodenoscopy, or EGD, must be performed if symptoms do not improve within 3 days. If the patient does not have oropharyngeal thrush, an EGD might be performed sooner as the etiology of the symptoms is less clear.

Herpes-simplex virus is another infectious cause of esophagitis, typically caused by HSV-1 that presents with multiple punched-out ulcers on endoscopy as opposed to white plaques or patches.

Pill-induced esophagitis can occur when patients attempt to swallow medications, but they become stuck in the esophagus and have a caustic effect. Potassium chloride, tetracyclines, and bisphosphonates are often culprits.

Hydroxyzine is a non-selective antihistamine that is used in the treatment of anxiety, alcohol withdrawal, pruritus, nausea/vomiting, preoperative sedation, and insomnia. It is not used for the treatment of narcolepsy.

Imipramine is a tricyclic antidepressant that can be used to treat enuresis (bedwetting) because it decreases the amount of stage three sleep (when most bedwetting occurs). Pharmacotherapy for enuresis should be used as last resort after behavioral therapy has failed.

Maprotiline is an atypical antidepressant that blocks norepinephrine uptake. It is sometimes used for symptomatic treatment of insomia, but Maprotiline is not used to treat narcolepsy

Major takeaway
Narcolepsy is a chronic neurological disorder characterized by symptoms of daytime sleepiness and cataplexy. The standard treatment for narcolepsy includes central nervous system stimulants.

Main explanation
This presentation is suggestive of narcolepsy, a chronic neurological disorder in which the regulation of the patient’s sleep-wake cycles is dysfunctional; it is characterized by excessive daytime sleepiness and cataplexy. Cataplexy is a brief episode of bilateral weakness that occurs without loss of consciousness and is initiated by some strong emotional stimulus. Additional symptoms may include sleep paralysis and frightening hallucinations either at the start of sleep (hypnagogic) or just before they awakening (hypnopompic). There is a strong genetic component associated with narcolepsy. Narcolepsy is most often treated with central nervous system stimulants such as modafinil or amphetamines.Modafinil is a psychostimulant that is FDA approved for the treatment of narcolepsy, shift work sleep disorder and excessive daytime sleepiness associated with obstructive sleep apnea. The exact mechanism of modafinil is unclear, but it increases the number of monoamines, specifically norepinephrine, serotonin, and histamine, in the brain.

Zolpidem is a non-benzodiazepine hypnotic that is used for the treatment of insomnia by effectively initiating sleep; it is not used for the treatment of narcolepsy.