Herpes Simplex Infections

Introduction 

Herpes simplex virus infections occur equally between the sexes throughout the year. 

-Penn State Students in State College are at high risk when they touch lesions of herpes

HSV-1 transmission typically occurs via oral-oral, oral-genital, or genital-genital contact.

HSV-2 lesions largely involve the genital tract, with the virus remaining latent in the sacral nerve root ganglia (S2–S5) 

Symptoms & Signs 

Both viral subtypes can cause genital and oral–facial infections

The infections caused by the two subtypes are clinically indistinguishable.

Gingivostomatitis and pharyngitis:   the most frequent clinical manifestations of primary HSV-1 infection; presents as small, grouped vesicles on an erythematous base, burning and stinging sensation, swollen and tender burning and stinging 

Genital: most genital infections are caused by HSV-2; presents with bilateral genital ulcerations and tender lymphadenopathy. 

Ocular disease: HSV keratitis presents with vision loss, pain, and discharge; it is a major cause of blindness from corneal scarring and opacity. 

Neonatal & Congenital infection: Neonatal HSV can present as excessive tearing, eye pain, conjunctival edema, vesicular lesions of the mouth, palate, tongue, seizures, irritability, fever, multiple organ failure

CNS Disease: Both viruses can cause encephalitis; the temporal lobe is often involved; it presents with 

the rapid onset of fever, headache, seizures, focal neurologic signs, and impaired consciousness

Bell’s Palsy: HSV-1 is a cause of Bell palsy (facial nerve paralysis)

Esophagitis & Proctitis: usually presents with dysphagia or odynophagia, fever, retrosternal chest pain 

Erythema multiforme: HSV infection is the most common cause of EM; Cutaneous eruptions occur 2 to 7 days after herpes simplex infection 

Diagnosis 

Diagnosis can be made by physical examination; Direct fluorescent antibody slide tests, viral culture, polymerase chain reaction 

Treatment 

Early antiviral therapy within 72 hours of symptom onset

Antiviral drugs: Acyclovir, Famciclovir, Valacyclovir 

Severe or frequent recurrences: Chronic suppressive therapy with antivirals 

Keratitis: The usage of topical corticosteroids may exacerbate the infection

Prevention 

Male circumcision is associated with a lower incidence of acquiring HSV-2 infection.

Prognosis 

Q. What is the most frequent sign of HSV reactivation disease? Herpes labialis 

Q. What is the most frequent etiologic agent of Erythema multiforme? Herpes simplex virus 

Q. What is the most common cause of fatal sporadic encephalitis in the United States? HSV-1 encephalitis 




Tourette Syndrome

Introduction

-Gilles de la Tourette syndrome is a chronic neuropsychiatric disorder characterized by multiple motor and phonic tics. 

-Tics are sudden, involuntary, rapid, uncontrollable, repetitive, nonrhythmic, stereotyped movements with no purpose. 

-Symptoms begin before 21 years of age, most often by the age of 11

-the course is one of remission and relapse.

-the disorder is more common in males than females 

Symptoms & Signs 

Tics typically start early, at 3–5 years of age, and peak around 9–12 years

Phonic Tics: Throat-clearing,gruting, barking, sniffing, hissing

Coprolalia: Vulgar or obscene speech 

Echolalia: Parroting the speech of others 

Echopraxia: Imitation of others’ movements 

Palilalia: Repetition of words or phrases 

Motor tics: Eye Blinking, facial grimacing, sniffing, hopping, jumping, and kicking, body gyrations, complex obscene gestures, neck jerking, shoulder shrugging 

Sensory tics: Tics consisting of pressure, tickling, and warm or cold sensations 

Behavioral disorders: Anxiety, obsessive-compulsive disorder, attention deficit disorder, depression 

Diagnosis 

Diagnosis is made based on history and physical examination

Laboratory tests are normal 

Treatment 

Behavioral therapy: Cognitive behavioral therapy, Habit reversal training 

Pharmacotherapy: 

α-Adrenergic agonists: the first-line therapies

Clonidine: Most frequent side-effects are sedation, orthostatic hypotension, constipation 

Guanfacine 

Antipsychotics: Risperidone, Aripiprazole,olanzapine, ziprasidone, Haloperidol, Pimozide 

Botulinum toxin A injections 

Tetrabenazine 

Prognosis 

-the disorder is chronic, with waxing and waning

-Majority will experience significant improvement by the end of adolescence (80%).


Restless Legs Syndrome

Introduction 

-Restless legs syndrome is a chronic, neurological movement disorder characterized by a feeling of needing to move the legs (dysesthesia), associated with abnormal sensations like unpleasant creeping, crawling, tingling, and itching. 

-Cause is unknown in most cases. 

-Known causes of RLS: iron-deficiency anemia, renal failure, alcohol before sleep, thyroid disease, pregnancy, and certain medications 

-Druginduced RLS 

Anti-nausea drugs: Metoclopramide, Prochlorperazine 

Anticonvulsants: Phenytoin, Droperidol 

Antipsychotic drugs: Haloperidol 

Antidepressants: Sertraline 

-The disorder seems especially common among pregnant women (1 in 5)

Symptoms & Signs 

-Irresistible urge to move the limbs with creeping or crawling sensations 

-Symptoms usually occur when patient is lying down or relaxing 

-Abnormal sensations are temporarily alleviated by movement, stretching, or massage 

-Symptoms are worse in the evening and first half of night 

Diagnosis 

Diagnosis is usually made on clinical grounds alone

Search for iron deficiency: Ferritin levels should always be measured

Treatment 

Non-Pharmacotherapy

– Stop aggravating medications, smoking, excessive alcohol consumption, coffee 

-Daily moderate exercise, massage

-cognitive behavioral therapy 

Pharmacotherapy

-RLS is treated by addressing the underlying cause 

-Oral iron sulfate in patients with levels ≤ 75 mcg/L (13.4 mcmol/L)

-Other medications: Pramipexole, ropinirole, rotigotine, gabapentin, Pregabalin, Levodopa, clonazepam, temazepam, opiates 

Dopaminergic therapy is the treatment of choice for severe cases but carries the risk of augmentation

Augmentation: the earlier onset or enhancement of symptoms; earlier onset of symptoms at rest; and a briefer response to medication.

RLS vs PLMS (Periodic Limb Movements of Sleep): 

-RLS tends to occur during waking and at sleep onset, whereas PLMs occur during sleep. 

-Patients with RLS sometimes also have PLMs, but patients with PLMs often do not have RLS. 

Prognosis 

Prognosis depends on the underlying cause

Q.Most common treatable cause of RLS: Iron deficiency 

Q.What is the most common complication of long-term dopaminergic therapy? Augmentation


Parkinson’s Disease

Introduction 

-Parkinson’s disease is a neurodegenerative disorder due to dopamine depletion in the substantia nigra and in the nigrostriatal pathway to the caudate and putamen. 

-the second most common age-related neurodegenerative disease, exceeded only by Alzheimer’s disease (AD)

-The mean age of onset of PD is about 60 years

-The cause remains largely unknown 

-The only known cause of PD: Genetic mutations 

-Occurs in all ethnic groups with equal sex distribution 

-Prior use of ibuprofen is associated with a decreased risk of developing Parkinson disease 

Symptoms & Signs 

rest tremor, rigidity (stiffness), bradykinesia (slowing), and gait dysfunction with postural instability. freezing of gait, speech difficulty, swallowing impairment, autonomic disturbances,

MOTOR FEATURES 

Cardinal features: Tremor (most conspicuous at rest, enhanced by stress)Rigidity, Bradykinesia(the most disabling symptom; a slowness of voluntary movement) 

Craniofacial: Masked facial expression (hypomimia), hypophonia, Dysphagia, Repetition of a phrase or word with increasing rapidity (palilalia), speech impairment 

Visual: blurred vision, Eyelid opening apraxia, hypometric saccades, impaired vestibuloocular reflex 

Musculoskeletal: Stooped posture, micrographia, dystonia, myoclonus, difficulty turning in bed

Gait: A loss of the normal automatic arm swinging, Shuffling, Short-stepped gait, freezing, festination  

NONMOTOR FEATURES 

Psychosis: Visual, auditory, olfactory, and tactile hallucinations 

Fatigue

Olfactory dysfunction: loss of smell 

Sensory disturbances: Pain 

Mood disorders: Depression (most common psychiatric disturbance seen in PD), anxiety, loss of motivation, 

Sleep disturbances: Rapid eye movement sleep behavior disorder (RBD), sleep fragmentation, early morning awakening, restless legs syndrome 

Autonomic disturbances

 Orthostatic hypotension

 Gastrointestinal disturbances Constipation, Dysphagia 

 Genitourinal disturbances Urinary difficulties 

 Sexual dysfunction: underactivity, hypersexuality 

Cognitive impairment/Dementia

Dermatologic: Seborrhea 

Diagnosis 

There are no diagnostic tests for PD 

Primarily a clinical diagnosis based on symptoms and signs 

Myerson Sign: Repetitive tapping (about twice per second) over the bridge of the nose producing a sustained blink response

Treatment 

PHARMACOLOGIC TREATMENT 

Dopamine Replacement Therapy 

Dopamine: Given the deficiency of dopamine, it would be nice if we could just give dopamine itself. However, dopamine does not cross the blood-brain barrier. 

Levodopa: 

Logic behind Levodopa-Carbidopa combination: 

Levodopa can cross the blood-brain barrier, but large doses are required because much of the drug is decarboxylated to dopamine in the periphery causing side-effects like nausea, vomiting, and orthostatic hypotension. 

Carbidopa is a dopamine decarboxylase inhibitor that does not cross the blood–brain barrier. It reduces the peripheral metabolism of levodopa, thereby increasing the amount of levodopa that reaches the brain.

-It is the most effective symptomatic treatment for PD 

-It controls classic motor features of PD, improves quality of life, and increases the lifespan

MAO-B inhibitors 

Selegiline, Rasagiline, Safinamide 

At lower doses, Selegiline and rasagiline are not associated with a cheese effect (hypertensive crisis), usually seen when MAO-B inhibitors are taken with tyramine-rich containing foods 

Side-effects: nausea, headache, confusion, hallucinations 

COMT Inhibitors 

-Tolcapone, Entacapone, Opicapone  

-Inhibitors of COMT prolong the elimination half-life of levodopa and enhance its brain availability.

Side-effects of Tolcapone: Severe diarrhea, Fatal hepatic toxicity; periodic monitoring of liver function required

Amantadine

-Antiviral drug effective in the treatment of influenza 

-it ameliorates dyskinesias resulting from prolonged levodopa therapy

-Side-effects: Livedo reticularis, weight gain; should always be discontinued gradually to prevent withdrawal-like symptoms 

Dopamine Agonists (DAs) 

Ergot DAs: Bromocriptine 

Nonergot DAs: Pramipexole, Ropinirole, Rotigotine, Apomorphine 

Due to their serious side-effects, the first generation dopamine agonists (bromocriptine, pergolide, cabergoline) were replaced by second generation agonists such as pramipexole, ropinirole, rotigotine. 

-Side-effects: Sedation with sudden unintended episodes of falling asleep, impulse-control disorders (compulsive eating, shopping, hypersexuality, pathologic gambling) 

Anticholinergics 

Trihexyphenidyl(most widely prescribed anticholinergic), benztropine, biperiden 

-Contraindicated in patients with prostatic hypertrophy, narrow-angle glaucoma, or obstructive intestinal disease 

Side-effects: Dryness of the mouth, constipation, urinary retention, cardiac arrhythmias, palpitations, mydriasis, agitation, restlessness. 

Antipsychotics

Olanzapine, Quetiapine, Risperidone, Clozapine 

-Clozapine can cause marrow suppression, necessitating weekly cell counts 

Antidepressants: selective serotonin-norepinephrine reuptake inhibitor (SNRI) or a selective serotonin reuptake inhibitor (SSRI), cognitive behavioral therapy 

Stimulants: Modafinil, methylphenidate 

Nonpharmacologic management: 

Exercise and physical therapy 

Speech therapy

Occupational therapy

Nutrition 

Cognitive behavioral therapy 

Deep Brain Stimulation 

Palliative care 

Prognosis 

The serum urate level may be a prognostic indicator in men—the rate of progression declines as the urate level increases.