Adult Movement Disorders Flashcards
A 40-year-old man has a family history of hereditary neurodegenerative disease and early death. His father died of a rapidly progressive dementia at the age of 50 and he has previously been told that he has the defective gene. He presents with personality change and non-purposeful, slow, rhythmic movements of his hands and face. A magnetic resonance imaging (MRI) indicates atrophy in the head of the caudate nucleus. Which one of the following neurotransmitter deficiencies is most likely to be responsible?
a. Dopamine in the substantia nigra
b. Substance P in the subthalamic nucleus
c. Acetylcholine and gamma-aminobutyric acid in the striatum
d. Serotonin in the globus pallidus
e. Glutamate in the cortex
c. Acetylcholine and gamma-aminobutyric acid in the striatum
Huntington’s disease is characterized by loss of striatal neurons resulting in reduced levels of choline acetyltransferase, glutamic acid decarboxylase, and GABA in the striatum resulting in a relative excess of dopamine causing a hyperkinetic movement disorder with writhing and jerking movements of the limbs (chorea). Dopamine antagonists, such as haloperidol, may be used to suppress chorea, but also carry the risk of provoking tardive dyskinesia. Dopaminergic drugs, such as L-dopa, bromocriptine, and lisuride, may unmask chorea but should not be used diagnostically as it may not abate.
A 43-year-old man has a father who died from Huntington’s disease. The son was tested and found to have the gene for Huntington’s disease. Which one of the following is true regarding the offspring of those with Huntington’s disease?
a. All children are at risk only if the affected parent is male
b. 1 in 10 are at risk only if the affected parent is female
c. 1 in 8 are at risk for the disease
d. 1 in 4 are at risk for the disease
e. 1 in 2 are at risk for the disease
e. 1 in 2 are at risk for the disease
Huntington’s disease is transmitted in an autosomal dominant fashion. The age at which the patient becomes symptomatic is variable and has no effect on the probability of transmitting the disease. The defect underlying this degenerative disease is an abnormal expansion of a triplicate repeat (CAG) sequence in the HTT gene on chromosome 4 (normally coding for the protein huntingtin). Normal individuals have between 6 and 34 copies of this CAG section; patients with Huntington’s disease may have from 36 to more than 100 repeats. People with the adult-onset form of Huntington’s disease typically have more than 36 CAG repeats in the HTT gene (although those with 36-39 still may not develop signs/ symptoms) and those with the juvenile form of the disorder tend to have more than 60 CAG repeats. Individuals who have 27-35 CAG repeats in the HTT gene do not develop Huntington’s disease, but they are at risk of having children who will develop the disorder. As the gene is passed from parent to child, the size of the CAG trinucleotide repeat may lengthen into the range associated with Huntington’s disease (36 repeats or more). Once expanded beyond 40 copies, the repeats are unstable and may further increase as they are passed on from one generation to the next. An increased number of repeats in successive generations can lead to earlier disease onset, a phenomenon termed anticipation.
Damage to the subthalamic nucleus is associated with which one of the following
a. Myoclonus
b. Dystonic tremor
c. Hemiballism
d. Levodopa-induced dyskinesia
e. Tardive dyskinesia
c. Hemiballism
A lesion of the subthalamic nucleus results in hemiballism, a form of dyskinesia in which the patient displays severe involuntary movements. It is believed to occur as a result of an imbalance in the output signals of the basal ganglia, with overactivity of the direct pathway relative to the indirect pathway. This is in contrast to Parkinson’s disease, where overactivity of the indirect pathway relative to the direct pathway results in bradykinesia.
Tardive dyskinesia is most likely the result of receptor changes causing hypersensitivity to which one of the following neurotransmitters?
a. Serotonin (5-HT)
b. Acetylcholine
c. Enkephalin
d. Dopamine
e. GABA
d. Dopamine
Tardive dyskinesia results from treatment with dopamine receptor blocking agents. Tardive syndromes are less frequently caused by atypical than by typical neuroleptics. The most common pat- tern of tardive dyskinesia is stereotyped and repetitive movement of the face (e.g., tonguethrusting and involuntary chewing movements is often accompanied by a feeling of restlessness). This akathisia may be localized and reported as a “burning” sensation, often of the genitals or mouth.
Which one of the following statements regarding dystonia is most accurate?
a. Isolated foot dystonia is very rare and may suggest an underlying Parkinsonian disorder or brain structural abnormality
b. Torticollis is the least common dystonia
c. Segawa’s disease is a primary dystonia responsive to antidopaminergic drugs
d. Trihexyphenidyl is the primary treatment for drug-induced dystonia
e. Blepharospasm is involuntary opening of eyelids resulting in paradoxical blinking
a. Isolated foot dystonia is very rare and may suggest an underlying Parkinsonian disorder or brain structural abnormality
Focal dystonias produce abnormal sustained muscle contractions in a single region of the body:
* Neck (torticollis): most commonly affected site with a tendency for the head to turn to one side.
* Eyelids (blepharospasm): involuntary closure of the eyelids that leads to excessive eye blinking, sometimes with persistent eye closure and functional blindness.
* Mouth (oromandibular dystonia): involun- tary contraction of muscles of the mouth, tongue, or face. * Hand (writer’s cramp).
Isolated foot dystonia is very rare and may suggest an underlying Parkinsonian disorder or brain structural abnormality. Generalized dystonia affects multiple areas of the body and can lead to marked joint deformities. Primary dystonia can be sporadic or heritable (e.g., DYT1 dystonia, Segawa’s disease). Secondary dystonia results from basal ganglia insults (stroke, demyelination, hypoxia, trauma), Huntington’s disease, Wilson’s disease, Parkinson’s syndromes, and lysosomal storage diseases. Acute or chronic (tardive) dyskinesias can occur with dopaminergic antagonists (e.g., antipsychotics, antiemetics). In addition to removing any offending drug, trihexyphenidyl is an anticholinergic drug which is used to manage chorea, dystonia and dyskinesias (by correcting the imbalance between dopamine and acetylcholine in the basal ganglia).
A 65-year-old man presents with difficulty getting out of chairs and problems walking over the last year with multiple falls. On examination, his face appeared mask-like with reduced blinking and slight drooling, and he had a pill-rolling tremor at rest bilaterally, and on passive movement demonstrated cogwheel rigidity. His handwriting became smaller towards the end of a sentence. There was no weakness, sensory problems, or abnormalities in his reflexes. There are no autonomic symptoms. He had a stooped posture and walked with a slow shuffling gait, with a noticeably reduced arm swing. Which one of the following statements regarding this condition is most accurate?
a. It may present with a 3 Hz rest pill rolling tremor
b. The major neuronal loss is in the substantia nigra pars reticularis
c. It is associated with a fluent aphasia
d. Loss of smell is a non-motor symptom of this disease
e. Dyskinesias are common in non- medicated patients
d. Loss of smell is a non-motor symptom of this disease
Idiopathic Parkinson’s disease is a neurodegenerative condition caused by progressive loss of dopaminergic cells in the substantia nigra pars compacta projecting to the striatum. This produces a hypokinetic movement disorder characterized by bradykinesia, rigidity and resting tremor. More specific symptoms include: a slow shuffling gait with a tendency to move progressively faster (festinating gait); micrographia; mask-like facial expression with reduced eye blinking; and difficulty getting out of a chair; quiet monotonous voice (hypophonia); muscle rigidity (lead-pipe rigidity); pill-rolling rest tremor 4-8 Hz, which combines with rigidity to produce “cogwheeling” on passive flexion by the examiner. Non-motor symptoms may also have a major impact on quality of life: drooling (reduced swallowing), dementia, REM sleep disorders, loss of smell, constipation, mood disorder (especially depression), orthostatic hypotension, bladder and erectile dysfunction. Dopamine cannot cross the blood-brain barrier, hence medical therapy must increase striatal dopamine by other means (e.g., prevent catecholamine breakdown [MAOI-B], provide the immediate precursor to dopamine [levodopa], or other dopaminergic receptor agonists).
Which one of the followings statements regarding Parkinson’s plus syndromes is LEAST accurate?
a. MSA-P (Striatonigral degeneration) is characterized by Parkinsonism with autonomic failure
b. Dementia with Lewy bodies is often associated with detailed visual hallucinations
c. Tremor is rare in progressive supranuclear palsy
d. Corticobasal degeneration may include cortical sensory loss and apraxia
e. MSA-C (olivopontocerebellar atrophy) is characterized by Parkinsonism with progressive ataxia
e. MSA-C (olivopontocerebellar atrophy) is characterized by Parkinsonism with progressive ataxia
Many other disorders present with Parkinsonian features early in their course, and the more characteristic features of some of these “Parkinson’s plus” syndromes (e.g., gaze paralysis in progressive supranuclear palsy or autonomic dysfunction in multiple system atrophy) may not become apparent until several years after symptom onset. An incorrect diagnosis of early Parkinson’s disease is probably made between 10% and 20% of the time, even among Parkinson’s disease specialists. An accurate early diagnosis of Parkinson’s disease is becoming increasingly important as the long-term effects of early treatment on natural history are better understood. Secondary Parkinsonism may be idiopathic, drug-induced, toxin-induced, due to cerebrovascular disease or structural lesions, or post-traumatic. Clinically similar to Parkinson’s disease, symptomatic Parkinsonism may be identified by history (e.g., medication history or exposure to toxins) or by symptoms and signs consistent with an underlying disorder. Clues suggesting secondary Parkinsonism include acute/subacute onset, symmetric symptoms, rapid progression or static course, poor response to dopaminergic drugs, history of exposure to causative drugs/toxins/ CNS infection/cerebrovascular disease, and signs of underlying metabolic or structural brain disease.
A 67-year-old man had idiopathic tremulous Parkinson’s disease diagnosed 15 years ago, and has had a 10-year history of progressive worsening in wearing-off phenomenon. Despite increasing the dose and frequency of levodopa this had still deteriorated, and higher doses induced peak-dose dyskinesias. High-frequency stimulation of which one of the following brain structures is most likely to improve his symptoms?
a. Unilateral STN
b. Bilateral STN
c. Unilateral Vim
d. Bilateral Vim
e. Bilateral GPi
b. Bilateral STN
A number of prospective and randomized trials comparing STN and GPi DBS have contributed to a better definition of the differences between these two targets. STN stimulation is superior for rigidity, bradykinesia, cost (medication reduction and less frequent battery change) and is more popular for tremor due to proximity to zona incerta. GPi stimulation is superior for dyskinesia, dystonia (including levodopa-unresponsive; STN only works for levodopa-responsive), cognition, mood and apathy, axial motor symptoms, does not adversely affect speech/swallowing, can be implanted unilaterally, and requires less frequent programming (initially). The motor benefits can be similar with each target, but STN offers greater benefit for off-symptoms, facilitates medication dose lowering and is most cost efficient, whereas dyskinesia suppression and longterm effects on postural stability and cognitive function favor GPi. STN stimulation may risk behavior and impulse control disorders, but medication reduction reduces these. FURTHER READING Fasano A, Lozano AM. Deep brain stimulation for movement disorders: 2015 and beyond. Curr Opin Neurol 2015;28:423-36.
A 25-year-old man has had motor tics since age 13. They seem to be getting worse, and now he also has involuntary obscene vocalizations. Which one of the following stimulation targets would you use in this patient?
a. Centromedian nucleus parafascicular complex of thalamus
b. Vim thalamus
c. Posterior hypothalamus
d. Subthalamic nucleus
e. Hippocampus
a. Centromedian nucleus parafascicular complex of thalamus
Tourette’s syndrome is defined by the onset of motor and vocal tics before 18 years of age that cannot be ascribed to another medical condition. Tics must occur multiple times over at least 1 year and must evolve over time. The first tics are usually observed around the age of 5 or 6, and tic severity peaks 4-5 years later, and is lowest in patients’ early 20s, coincident with frontal lobe maturation. Tics are worsened by heightened emotional states, stress, and fatigue. The tics of Tourette’s syndrome are commonly accompanied by attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). In Tourette’s syndrome, obsessions center on concerns with symmetry, fear of violent thoughts, and a need to perform activities in a particular manner (rather than fears of contamination and checking seen in primary OCD). These obsessions may lead to self-injurious behavior. There is evidence that it shows a sex-linked autosomal dominant mode of inheritance, and is due to dysfunction in the corticostriatalthalamocortical loop. The most commonly used targets for DBS have been the thalamic nuclei (centromedian nucleus-parafascicular complex and ventral oral nuclei) followed by either the limbic (anteromedial) or motor (posteroventral) regions of GPi. A double-blind, randomized crossover trial on GPi DBS has reported a significant improvement in tic severity, with an overall acceptable safety profile. FURTHER READING Fasano A, Lozano AM. Deep brain stimulation for movement disorders: 2015 and beyond. Curr Opin Neurol 2015;28:423-36.
A 22-year-old male is involved in a road traffic collision and sustains a significant traumatic brain injury. CT head shows traumatic subarachnoid hemorrhage and hemorrhagic contusions extending into the basal ganglia. After a long period of rehabilitation he is left with a residual left arm tremor. Which one of the following could be consid- ered to manage his tremor?
a. Motor cortex stimulation
b. VIM thalamic stimulation
c. STN stimulation
d. Red nucleus stimulation
e. Ventral striatal/ventral internal capsule
stimulation
b. VIM thalamic stimulation
DBS of the ventro-intermedius nucleus (Vim) of the thalamus is an effective treatment for essential tremor, tremor dominant PD and other types of tremor. In essential tremor, a loss of benefit is sometimes observed over time. In both shortand long-term studies, dysarthria and disequilibrium are the most frequent reported adverse effects, especially with bilateral stimulation. The very mild cerebellar ataxia displayed by ET patients may also be improved by the stimulation of the posterior subthalamic area (STA), beneath the inferior border of the Vim, where the dentato-thalamic tract runs—conversely strong stimulation worsens cerebellar side effects. FURTHER READING Fasano A, Lozano AM. Deep brain stimulation for movement disorders: 2015 and beyond. Curr Opin Neurol 2015;28:423-36.
Which one of the following targets is most commonly used for the treatment of dystonia?
a. GPi
b. Vim thalamus
c. Vo thalamus
d. STN
e. Nucleus accumbens
a. GPi
GPi DBS in isolated dystonias (either generalized or segmental) is supported by strong evidence of success, with improvement. Improvement is sustained up to 10 years after surgery, although some patients need the implantation of additional GPi electrodes. In addition, there are encouraging results in cervical dystonia, myoclonus-dystonia and tardive dystonia, in which the outcome of DBS is usually excellent, rapid and sustained. Case reports have also shown that cranial/cervical dystonias may not recur when DBS has stopped working (for a variety of reasons) suggesting chronic changes to circuits. FURTHER READING Fasano A, Lozano AM. Deep brain stimulation for movement disorders: 2015 and beyond. Curr Opin Neurol 2015;28:423-36.
Which one of the following statements regarding thalamotomy is LEAST accurate?
a. It is most appropriate for those with predominantly unilateral symptoms
b. Lesions placed to laterally may result in contralateral weakness
c. Bilateral thalamotomy is the treatment of choice in bilateral tremor dominant Parkinson’s disease when deep brain stimulation is not possible
d. Speech disturbance is a common problem
e. Lesions placed too posteriorly may cause numbness and paresthesias of the mouth
c. Bilateral thalamotomy is the treatment of choice in bilateral tremor dominant Parkinson’s disease when deep brain stimulation is not possible
The best candidates for thalamotomy are patients with tremor-predominant PD or those with incapacitating benign essential tremor. Less predictable outcomes are seen with tremor and hemiballismus/chorea due to damage of the cerebellar tracts from cerebrovascular accidents, trauma or multiple sclerosis, and primary and secondary dystonias. It is important to confirm the clinical diagnosis of idiopathic PD or benign essential tremor since Parkinson’s plus syndromes have a much poorer prognosis after thalamotomy. Evidence of cognitive decline, speech disorders, serious systemic disease, and advanced age are also considered contraindications to surgery. Specific complications of thalamotomy are due to inaccurate lesion placement or overly large lesions. Lesions placed too laterally may result in contralateral weakness due to injury of the posterior limb of the internal capsule (face and arm). Lesions placed too posterior may cause contralateral hemisensory deficits due to injury of the VC nucleus (e.g., numbness or paresthesias of the mouth or fingers). A significant proportion have transient dysarthria or dysphasia, and transient confusion and may persist permanently in some. Left thalamic lesions are associated with an increased risk for deficits in learning, verbal memory and dysarthria while right thalamic lesions are associated with impaired visuospatial memory and nonverbal performance abilities. Bilateral thalamotomies are associated with deficits in memory/cognition and speech problems (e.g., hypophonia, dysarthria, dysphasia, and abulia) in up to 60%, hence should not be undertaken routinely—where they must be done it should be staged and slight variation in the target coordinates between sides may reduce major side effects.
