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.



Essential Tremor

Introduction

-Essential Tremor (ET) is the most common movement disorder 

-It is characterized by high-frequency action tremor of the hands, forearms, head, and voice. 

-Family history is often present with autosomal dominant pattern of inheritance

-It is a chronic and slowly progressive disorder 

-It is postural and kinetic in nature 

-It can present in childhood but often -often starts in the third or fourth decade of life 

-Absence of other etiologic factors and neurologic signs: Alcohol, Parkinsonism, medications, hyperthyroidism 

Symptoms & Signs 

-The tremor typically starts from either hands or forearms 

-It is typically bilateral and symmetric but can be asymmetric 

-The tremor is not present at rest, but emerges with action. 

-Tremor can be postural (occurring with outstretched arms), or kinetic (occurring during action such as writing) 

-In severe cases, interferes with activities of daily living, handwriting, vocalization 

-Alcohol provides short-lived relief 

-Other than the tremor, neurologic examination should be normal

Diagnosis 

-ET is a clinical diagnosis based on history and physical examination 

-Labs to rule out thyroid dysfunction, Wilson disease, electrolyte disturbances 

-A DaT scan is normal, whereas it is abnormal in Parkinson’s disease.

Treatment 

If the tremor is mild and non-disabling, treatment may not be required. 

Behavioral: Stress reduction, Caffeine avoidance 

Occupational therapy: Adaptive utensils 

Pharmacotherapy: 

First-line agents: Propranolol, Primidone

Second-line agents: Gabapentin, topiramate, zonisamide

Surgical therapies: Unilateral thalamotomy, DBS (Deep Brain Stimulation) in the ventral intermediate (VIM) nucleus of the thalamus, High-frequency thalamic stimulation

Injections: Botulinum injections  

Prognosis 

-ET is a slowly progressive disorder and remains mild in the majority of cases. 

-Patients with essential tremor have a higher risk of developing Parkinson disease than the general population.


Sturge Weber Syndrome

Introduction

Sturge-Weber syndrome (SWS) is a sporadic congenital neurovascular disorder 

– It consists of facial port wine nevus involving the upper part of the face (in the first division of cranial nerve V) and capillary-venous malformations affecting the brain and eye. 

-SWS is caused by somatic mosaic mutations in the GNAQ gene. 

-It is not a heritable disorder. 

Symptoms & Signs 

Vascular: Port wine stain on one side of the face, (In one-quarter of the cases the nevus is bilateral), leptomeningeal vascular malformation

Neurologic features: Seizures, Focal neurologic deficits, hempiparesis, intellectual disability 

Ocular features: Glaucoma, capillary-venous vascular malformations of the conjunctiva, episclera, choroid, and retina 

Visual features: Homonymous hemianopia 

Diagnosis 

Plain Skull X rays: Cortical double-contoured calcifications “tramline” calcifications 

CT, MRI brain: Cortical atrophy 

Glaucoma testing 

EEG: depression of voltage over the involved area in early stages

Treatment 

No specific, effective treatment exists for SWS.

Port wine stains: Selective photothermolysis 

Choroidal hemangioma: laser photocoagulation or radiotherapy 

Seizures: Antiepileptics 

Glaucoma: Medications, surgery 


Neurofibromatosis

Introduction

-Neurofibromatosis (NF) is a multisystem, autosomal dominant disorder 

-The most common forms are NF1 and NF2.

-NF-1 is associated with gene mutations on chromosome 17 and NF-2 on chromosome 22.

-These mutations result in loss of function of neurofibromin, which leads to increased protooncogene ras activity in neurocutaneous tissues, culminating in tumorigenesis. 

Symptoms & Signs 

Manifestations of NF Type 1 

Neurologic: peripheral and spinal neurofibromas 

Ophthalmologic: optic gliomas and iris hamartomas such as Lisch nodules

Dermatologic: Café au lait spots: well-circumscribed, light to dark brown macules with smooth borders); freckling in the axillary or inguinal regions; glomus tumors in the tips of the fingers and toes

Skeletal: Sphenoid wing dysplasia, scoliosis, macrocephaly, short stature, and pseudoarthrosis 

Vascular: Stenoses of renal and intracranial arteries

Endocrine: Pheochromocytoma, carcinoid tumors, and precocious puberty)

Manifestations of NF2 Type 2 

Otolaryngeal: Bilateral vestibular schwannomas (acoustic neuromas) leading to deafness, tinnitus, or vertigo

Neurologic: cranial meningiomas, spinal tumors, Distal, symmetric, sensorimotor neuropathy 

Dermatologic: Café-au-lait spots (less common than NF1)

Muscular: Muscular weakness or wasting

Diagnosis 

-Diagnosis is typically made during childhood based on the characteristic clinical features 

-Genetic testing for couples considering having children 

-CT or magnetic resonance imaging is useful for the diagnosis of optic glioma 

-Slit-lamp examination is useful for the diagnosis of Lisch nodules 

-Patients with NF2, as well as their family members, should undergo complete audiological testing to assess the level of hearing

Treatment 

-Café-au-lait spots and freckling: lasers, intense pulsed radiofrequency 

-Neurofibromas: Surgical excision, Carbon dioxide laser 

-Scoliosis, long bone dysplasia: Orthopedic interventions 

-Optic gliomas: chemotherapy with vincristine, cisplatin 

Prognosis 

NF1 patients have an increased risk of developing gastrointestinal stromal tumors.Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors; in contrast, malignant transformation of superficial neurofibromas is extremely rare