Movement Disorders Case File

Movement Disorders Case File

Eugene C. Toy MD, Donald Briscoe, MD, FA  AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA  AFP, FACG

Case 55

A 46-year-old woman presents to your office complaining of a right hand tremor that has been steadily worsening over the past 2 years. She works as a literary agent and states that this tremor is increasingly impairing her ability to work, since this is affecting her dominant hand. She tells you in a slightly quivering voice, "I am often required to take my clients out to lunch, and I get embarrassed when I cannot eat and drink normally. Sometimes, I cannot even drink from a cup without shaking:' She finds that a glass of wine with her meal sometimes helps minimize the tremor. On examination, her blood pressure is 125/85 mm Hg, her pulse is 84 beats/min, and her respiratory rate is 16 breaths/min. Neurologic examination reveals a mild head tremor, but no resting tremor of the hands. When she holds a pen by its tip at arm's length however, a coarse bilateral tremor becomes readily visible, which is more pronounced on the right side. The rest of her examination is unremarkable.

⯈ What is the most likely diagnosis?

⯈ What further evaluation needs to be performed?

⯈ What pharmacologic interventions may be beneficial?

ANSWER TO CASE 55:

Movement Disorders

Summary: A 46-year-old woman presents with a classic essential tremor. It manifests during action and remits when the limb is relaxed, unlike the tremor of Parkinson disease. She is very disturbed by the tremor as it is leading to a great deal of social embarrassment, often interfering with her work. She has found that alcohol helps to reduce the symptoms.

• Most likely diagnosis: Essential tremor.
• Further evaluation necessary: Ensure that medications, thyroid disease, alcohol, or other neurologic diseases are not causing the tremor.
• Beneficial pharmacotherapy: Propranolol, primidone, and gabapentin.

ANALYSIS

Objectives

1. Become familiar with the presenting signs and symptoms of the most common movement disorders.
2. Become familiar with the management of common movement disorders.
3. Be able to gauge the severity of disease and understand potential side effects of therapies.

Considerations

Essential tremor is the most common of all movement disorders, affecting 1.3% to 5% of persons over the age of 60. A complete history is crucial in making an appropriate diagnosis of essential tremor. It usually appears after the age of 50 and often interferes with common tasks and activities of daily living. Close to one-half of all patients with an essential tremor have a family history of tremor, although this is not a strict criterion for diagnosis. Tremor is often attenuated with the use of alcohol. It is important to ask about the consumption of caffeine, cigarette smoking, stimulant use ( eg, pseudoephedrine) and to inquire about prescription medications (eg, fluoxetine, lithium, theophylline, valproic acid, haloperidol, metoclopramide) that are known to cause or enhance physiologic tremor.

When essential tremor is suspected, the patient should be observed while performing goal-directed tasks such as finger-to-nose testing or reaching for and drinking from a glass. Evaluating handwriting samples can help to identify the time of tremor onset and progression of disease. Tremor commonly affects the hands in 95%, the head in 34%, and the lower extremities in 20% of patients. In evaluating patients who present with tremor, thyroid and liver function tests are indicated. Additional testing includes serum ceruloplasmin and copper levels when patients are less than age 40 for evaluation of Wilson disease, a disorder of copper metabolism.

Pharmacotherapy constitutes the main approach to treatment of essential tremor. First-line therapies include the β-blocker propranolol and the anticonvulsant primidone, which are equally efficacious in reducing tremor symptoms. Topiramate and gabapentin are other anticonvulsants that can be used as second-line agents. The patient's report of symptoms and functional ability, rather than the

severity of tremor detected on physical examination, should serve as guides for adjustment of therapy. It is also important to monitor patients for side effects of these medications. Propranolol is associated with fatigue, headaches, bradycardia, impotence, and depression. Primidone can cause an acute reaction consisting of nausea, vomiting, confusion, or ataxia in many patients. As with therapy for Parkinson disease, both deep brain stimulation and ablation of the ventral intermediate nucleus of the thalamus (Vim nucleus) are effective in patients with tremor that is refractory to medical treatment.

Approach To:

Movement Disorders

DEFINITIONS

CHOREA: Unpredictable, involuntary, irregular, brief movements that are jerky, writhing, or flowing.

HYPERKINESIAS: Movement disorders characterized by extra or exaggerated movements.

HYPOKINESIAS: Movement disorders characterized by overall slowness of movement (bradykinesia), lack of movement (akinesia), or difficulty in initiating movement.

CLINICAL APPROACH

A movement disorder can be defined as any condition that disrupts normal voluntary movement of the body or that consists of one or more abnormal movements. They can be classified as hypokinesias or hyperkinesias (Table 55-1). Although less frequently encountered by family physicians than other chronic diseases, they

are fairly common, especially in the aging population. Parkinson disease, for example, affects 1 % of those over 60 and 2% of those over 85 years.

Movement disorders present a special challenge to family physicians for many reasons. Signs and symptoms can often be subtle and may not be detected on routine physical examinations. The normal process of aging is associated with changes in movement that may be mistaken for a more serious problem. Laboratory and radiologic testing are often of limited value in the diagnosis of movement disorders.

Management of tremor is equally challenging. Movement disorders have a great impact on other medical conditions as well as on the psychological well-being of patients and their families. Educating both the patient and family about the disease process and available treatment options can provide better understanding and management of the disorder. Although pharmacotherapy and surgeries are often administered by specialists, family physicians play an integral role in helping patients to cope with the broad impact of their disease.

Parkinson Disease

Parkinson disease is the most common neurodegenerative disease, and can cause significant disability and decreased quality of life. Symptoms appear as neurons and dopamine are lost from the substantia nigra (part of the basal ganglia) and intracytoplasmic inclusions (Lewy bodies) proliferate. Dopamine depletion in the substantia nigra ultimately leads to increased inhibition of the thalamus and decreased excitation of the motor cortex, which gives rise to parkinsonian symptoms such as bradykinesia. The cardinal physical signs of the disease are distal resting tremor, micrographia, cogwheel rigidity, bradykinesia, postural instability, shuffling gait, and asymmetric onset. Expressive language is typically not affected, but clarity and volume of speech may be compromised.

Pharmacotherapy is the mainstay of treatment for Parkinson disease, and has been shown to reduce both morbidity and mortality. The goals of treatment are to slow down progression and symptomatic therapy. For symptomatic early disease, first-line treatments are levodopa for motor impairment, dopamine agonists such as pramipexole and ropinirole to lower risk of motor complications, and monoamine oxidase type B (MAO-B) inhibitors. Amantidine may be used early on in the disease course but has limited evidence in improving outcomes. Anticholinergics (eg, benztropine, trihexyphenidyl) can also be utilized in young patients with severe tremor, but their use is often limited by side effects.

Tremor is best treated with dopamine agonists, levodopa, and anticholinergics. For motor fluctuations and dyskinesia, dopamine agonists and/or MAO-B inhibitors (eg, selegiline, rasagiline), or catechol-O-methyltransferase (COMT) inhibitors (eg, entacapone, tolcapone) can be added. Deep brain stimulation of the subthalamic nucleus has been shown to ameliorate symptoms in patients with advanced disease. Physical therapy and exercise may have modest benefits in slowing a patient's functional disability in Parkinson disease.

Common comorbid problems associated with Parkinson disease include depression, dementia, fatigue, excessive daytime sleepiness, and psychosis. Hallucinations affect up to 40% of patients with Parkinson disease. Psychosis is usually drug-induced and can be managed initially by reducing the dose of antiparkinsonian medications. In patients with debilitating psychotic symptoms and hallucinations, antiparkinsonian drugs may be discontinued in the reverse order of their effectiveness. Anticholinergics should be stopped first, followed by amantadine, then COMT inhibitors, and dopamine agonists. Discontinuing levodopa is typically not an option for most patients with Parkinson disease; however, dose reduction may be considered as a last resort to minimize symptoms. Consultation with a subspecialist for optimal medical management is often required. Since the functional impairment of Parkinson disease is progressive, discussion of advance directives is appropriate with all patients. Education and support are important ways patients can cope with their illness.

Tourette Syndrome

Tourette syndrome (TS) is the most common tic disorder, usually developing during childhood or early adolescence. Inheritance through an autosomal dominant pattern is thought to play a major role in its etiology. The diagnosis requires the presence of vocal tics such as grunting and multiple motor tics occurring several times a day for at least 1 year, onset generally between 2 and 15 years but no later than age 21, and having tics that cannot be explained by other medical conditions or medication side effects. Additionally, a family history of tics or similar symptoms also supports the diagnosis of TS. There are a number of different types of tics ranging from simple noises to echolalia (repetition of words), coprolalia (excessive use of obscene words), and palilalia (repetition of phrases or words with increasing rapidity). Tics may be temporarily suppressed during mental concentration but generally worsen during periods of stress, excitement, boredom, or fatigue. The majority of affected children also suffer from coexisting attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), learning disorder, conduct disorder I oppositional defiant disorder, or migraine headaches.

Education and counseling of patient and family is most important, and may be the only treatment necessary. Explanation of tics, obsessions, and compulsions, and appreciation that these are not voluntary to patients, family, teachers, and coworkers is often very helpful. Patients frequently will suppress tics most of day and need to "release" tics upon return from school or work.

Pharmacotherapy should be considered if there is continued functional impairment despite education and behavioral therapy. Treatment of comorbid ADHD and OCD can reduce Tourette symptoms. Clonidine is considered the first-line treatment due to its long-term safety and its ability to improve symptoms of comorbid ADHD and OCD. Another a-receptor blocker, guanfacine, appears safe and effective for tics in patients with ADHD, but can cause significant hypotension and must be dosed cautiously.

Neuroleptics including pimozide and haloperidol are more effective for tics than clonidine but have greater risk of long-term side effects. Botulinum toxin injection into the affected muscles may be effective for the treatment of refractory phonic tics. Deep brain stimulation surgery is a final option available for refractory symptoms and requires subspecialty evaluation.

Huntington Disease

The most common cause of chorea among adults occurs is Huntington disease. Huntington disease is inherited in an autosomal dominant pattern, and affects men and women in equal numbers. It is caused by a trinucleotide (CAG) expansion in the Huntington gene located on chromosome 4. Onset may be at any age, although symptoms first appear between 35 and 50 years with progressive neuronal loss and dysfunction over the following 10 to 20 years. The two types of movement abnormalities pathognomonic for Huntington disease are chorea and abnormal voluntary movements. The presence of chorea is required at the time of diagnosis of Huntington disease. Initially, chorea involves mostly the face, trunk, and limbs. With time, the chorea becomes more widespread and affects the diaphragm, larynx, and pharynx. Abnormal voluntary movements include uncoordinated fine motor movements, gait disturbances, abnormal eye movements, dysarthria, dysphagia, and rigidity. Difficulties with voluntary movements get worse with time. Weight loss and cachexia are common among Huntington disease patients caused by the hyperkinetic movements and altered cellular metabolism leading to increased energy expenditure. Cognitive problems include difficulties with memory, visuospatial abilities, and poor judgment. A global dementia may be present in patients with advanced disease. The most common psychiatric problem is depression, which affects up to one-half of patients. Patients with Huntington disease are at significantly higher risk for suicide.

There is currently no treatment available to slow the progression of Huntington disease. Treatment should target the prevalent signs and symptoms, and be adjusted according to disease severity. Physiotherapy for gait and balance issues, a high calorie diet for increased metabolic requirement, and speech and swallowing therapy for managing dysphagia and aspiration are few of the supportive measures available for Huntington disease patients. Tetrabenazine, a dopamine depleting agent, can be helpful for chorea but has limited outcomes data. Side effects of tetrabenazine include depression, sedation, akathisia, and parkinsonian symptoms. Chorea that is unresponsive to tetrabenazine can be treated with neuroleptics. Benzodiazepines and antidepressants may be indicated for insomnia, anxiety, and depression. The primary counseling responsibility of the family physician is to understand the role of genetic testing and to offer it to affected and asymptomatic individuals in a responsible manner. Optimal care usually requires input from a multidisciplinary team which includes neurologists and therapists.

CASE CORRELATION

• See also Case 32 (Dementia).

COMPREHENSION QUESTIONS

55.1 An 18-year-old male patient is noted to have motor tics and involuntary, obscene vocalizations. Which of the following medications is indicated in the treatment of this disorder?

A. Trihexyphenidyl

B. Phenytoin

c. Carbamazepine

D. Haloperidol

E. Levodopa

55.2 A 21-year-old woman develops auditory hallucinations and persecutory delusions over the course of 3 days. She was hospitalized and started on haloperidol 2 mg three times daily. Within a week of treatment, she developed stooped posture and a shuffling gait. Her head was slightly tremulous and her movements became slowed. Her medication was changed to thioridazine, and trihexyphenidyl was added. Over the next 2 weeks , she became much more animated and reported no recurrence of her hallucinations. Which of the following is the most likely diagnosis?

A. Hyperparathyroidism

B. Adverse effect of neuroleptic

C. Encephalitis

D. Hypermagnesemia

E. Tourette syndrome

55.3 Which of the following represents the decrement in speech commonly exhibited by the patient with parkinsonism?

A. Progressively inaudible speech

B. Neologisms

C. Expressive aphasia

D. Receptive aphasia

E. Word salad

55.4 A 67-year-old woman with known Parkinson disease is brought to the clinic by her health-care provider. She is confined to a wheelchair and completely dependent on others. You notice large grossly abnormal movements in both the arms and legs. The patient has to be strapped to the wheelchair to avoid falling out and can't keep her shoes on due to the jerking movements. Bed rails have had to be installed on her bed to prevent her from falling out at night. She is not able to tell the correct month or the year. She has not had a change in her medication in 6 months. Which of the following medication adjustments would benefit her most?

A. Add haloperidol.

B. Decrease levodopa/carbidopa.

C. Increase levodopa/carbidopa.

D. Add donepezil.

E. Add entacapone.

ANSWERS

55.1 D. The clinical scenario described is associated with Tourette syndrome. A variety of drugs may help suppress the tics that are characteristic of this syndrome. These include haloperidol, pimozide, trifluoperazine, and fluphenazine. Antiepileptics such as carbamazepine and phenytoin are not useful. Levodopa is the drug of choice in treating advanced Parkinson disease. Trihexyphenidyl and benztropine are useful in suppressing the parkinsonism that may develop with haloperidol administration, but are not useful in the management ofTourette syndrome.

55.2 B. Butyrophenones, the most commonly prescribed of which is haloperidol, routinely produce some signs of parkinsonism if they are used at high doses for more than a few days. This psychotic young woman proved to be less sensitive to the parkinsonian side effects of thioridazine than she was to haloperidol. Adding the anticholinergic drug trihexyphenidyl may have also helped to reduce the patient's symptoms.

55.3 A. Language is not disturbed in Parkinson disease, as it is with aphasias. The clarity and volume of speech is what suffers. Handwriting is similarly disturbed, as the patient has increasingly smaller and less legible penmanship as he or she continues to write. This is referred to as micrographia.

55.4 B. The patient is suffering from dyskinesias from too much levodopa/carbidopa. Stopping levodopa/carbidopa is usually not an option for most patients; however, a reduction of the medication would be of the most benefit to her. Haloperidol would be a good choice if the patient was suffering from hallucinations. Donepezil is a medication used primarily for Alzheimer dementia and has no use in Lewy body dementia. Entacapone is a medication to enhance levodopa/carbidopa.

CLINICAL PEARLS

⯈ Movement disorders have a profound impact on the quality of life of patients and their families. Family physicians should become adept at counseling patients about prognosis and the availability of support groups and community resources.

⯈ The management of certain movement disorders including Parkinson disease is rapidly changing. It is important to find the latest information about emerging and alternative therapies, and to seek the help of a specialist when required.

REFERENCES

Crawford P, Zimmerman EE. Differentiation and diagnosis of tremor. Am Fam Physician. 2011;83(6): 697-702. 

Gazewood JD, Richards DR, Clebak K. Parkinson disease: an update. Am Fam Physician. 2013;87( 4): 267-273. 

Kurlan R. Tourette's syndrome. N Engl ] Med. 2010;363:24:2332-2338. 

Novak MJ, Tabrizi SJ. Huntington's disease. BM]. 2010;340:c3109. 

Olanow C, Schapira AV, Obeso JA. Parkinson's disease and other movement disorders. In: Kasper D, Fauci A, Hauser S, et al., eds. Harrison's Principles of Internal Medicine. 19th ed. New York, NY: McGraw-Hill Education; 2015. Available at: http://accessmedicine.mhmedical.com. Accessed May 25, 2015.

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