ARTICLE 1: PRODROMAL α-SYNUCLEINOPATHIES
Lana M. Chahine, MD, FAAN. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1268–1280.
PURPOSE OF REVIEW
This article describes prodromal α-synucleinopathies.
The pathology underlying α-synucleinopathies, which include Parkinson disease, multiple system atrophy, and dementia with Lewy bodies, begins years before the presence of the full syndrome that is the basis for the clinical diagnosis of each of these disorders. This “prodromal” phase may manifest with various signs or symptoms. In addition to individuals in the prodromal phase, some individuals are asymptomatic but are at risk for α-synucleinopathies owing to genetic predisposition or other risk factors.
Clinicians are increasingly seeing patients in the clinical setting who are prodromal or at risk for α-synucleinopathies, and this article reviews the approach to these patient populations, which includes identifying clinical features, assessment, and counseling.
- In determining an individual’s risk for Parkinson disease, behavioral/environmental risk factors, signs and symptoms, and biomarker changes are best considered in combination.
- Although several environmental and behavioral factors, including some medications, have been identified as increasing the risk of Parkinson disease, none of these medications should necessarily be prescribed or withheld from patients until further studies link these factors as being causal in Parkinson disease.
- Both the clinical history and neurologic examination are an important part of the assessment of individuals who may be at risk or prodromal.
- While dysautonomia is necessary for the diagnosis of multiple system atrophy, the presence of mild dysautonomia in someone with other prodromal features does not necessarily imply a multiple system atrophy diagnosis and can occur in people who develop Parkinson disease or dementia with Lewy bodies.
- Rapid eye movement (REM) sleep behavior disorder that occurs in the absence of secondary causes (idiopathic or isolated REM sleep behavior disorder) is highly specific of future risk of Parkinson disease, dementia with Lewy bodies, or multiple system atrophy.
- Based on current evidence, use of biomarkers to identify individuals with prodromal features would be best confined to the research context and is not yet appropriate in the clinical setting.
- Criteria for identifying prodromal Parkinson disease and prodromal dementia with Lewy bodies are useful for research but are not ready to be applied clinically for diagnostic or prognostic purposes.
- Longitudinal follow-up of individuals who are prodromal or at risk for an α-synucleinopathy may show an evolution of parkinsonism, cognitive changes, and other signs and symptoms, which may culminate into the clinical syndromes that constitute diagnostic criteria for Parkinson disease, dementia with Lewy bodies, or multiple system atrophy.
- In individuals at risk or prodromal for an α-synucleinopathy, currently no treatments are proven to prevent progression to a diagnosed disorder. However, several modifiable risk factors have been identified, and basic risk factor reduction and modification should be instituted where appropriate.
ARTICLE 2: DIAGNOSIS AND MEDICAL MANAGEMENT OF PARKINSON DISEASE
Avner Thaler, MD, PhD; Roy N. Alcalay, MD, MS. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1281–1300.
PURPOSE OF REVIEW
Parkinson disease (PD) is a common neurodegenerative movement disorder, the prevalence of which is rising as the world population ages. It may present with motor and nonmotor symptoms, and symptomatic treatment significantly improves quality of life. This article provides an overview of the workup and differential diagnosis for PD and reviews genetic and environmental risk factors and current treatments.
Novel treatments for the motor (eg, fluctuations and off times) and nonmotor (eg, hallucinations and orthostatic hypotension) complications of PD have been approved in recent years. In addition, with recent advances in our understanding of the genetics of PD, significant research is focusing on identifying at-risk populations and introducing genetically targeted interventions (precision medicine).
PD is a heterogeneous neurodegenerative movement disorder. Affected individuals may receive substantial symptomatic relief from nonpharmacologic, pharmacologic, and surgical interventions. Although no intervention to modify the progression of PD is currently available, precision medicine and modulation of the immune system are a major focus of ongoing research.
- Older age and male sex are the most established risk factors for Parkinson disease (PD). The most established environmental risk factor for PD is pesticide exposure.
- The seven genes clearly associated with PD risk are SNCA, LRRK2, and VPS35 (dominant); PRKN, PINK1, and DJ-1 (recessive); and GBA (risk factor).
- The definitive diagnosis of PD is based on pathology. The two key required criteria are atrophy of dopaminergic cells in the substantia nigra and accumulation of α-synuclein.
- The clinical diagnosis of PD was historically based on motor symptoms. More recently, nonmotor symptoms were added to the criteria to improve accuracy.
- Postural instability, which is a feature of parkinsonism, is not a part of the International Parkinson and Movement Disorders Society criteria for PD diagnosis as it usually appears at later stages of PD.
- Clinical red flags raise suspicion to an alternative diagnosis, most often multiple system atrophy, progressive supranuclear palsy, or dementia with Lewy bodies.
- The Hoehn and Yahr scale is often used to capture the severity and progression of motor symptoms of PD. The Movement Disorders Society Unified Parkinson’s Disease Rating Scale is used to quantify disease severity.
- The diagnosis of PD is primarily clinical. Ancillary diagnostic tests can be useful when the clinical diagnosis remains unclear.
- MRI or other structural imaging may detect causes of secondary parkinsonism, such as hydrocephalus or stroke.
- Dopamine transporter single-photon emission computed tomography may be helpful in detecting dopamine deficiency but is less useful in tracking the progression of intermediate or advanced stages of PD or in distinguishing PD from other neurodegenerative parkinsonian syndromes.
- Exercise and physical activity should be recommended for all patients with PD.
- No evidence exists that early pharmacologic (eg, levodopa) treatment of Parkinson disease has disease-modifying properties. However, neither does evidence exist for the benefit of delaying pharmacologic treatment.
- Comparing levodopa to dopamine agonists and monamine oxidase type B inhibitors has indicated that although all three therapies are efficacious, levodopa treatment is best tolerated and maximizes improvement in mobility scores.
- When impulse control disorder occurs, reduction in the dosage of dopamine agonist therapy is warranted; however, this might be complicated by the development of a dopamine agonist withdrawal syndrome.
- When motor symptoms advance, a key consideration is to reduce the motor off time and fluctuations. Continuous levodopa administration or deep brain stimulation should be considered.
- Careful adjustment of the dopaminergic treatment is a logical first step in the treatment of nonmotor symptoms in PD.
- Hallucinations in PD may significantly impair quality of life and limit the use of dopaminergic intervention. Careful management of hallucinations is indicated.
- Although the link between rapid eye movement (REM) sleep behavior disorder and PD is well established, evidence on effective management of REM sleep behavior disorder is insufficient.
ARTICLE 3: SURGICAL THERAPIES FOR PARKINSON DISEASE
Ashley E. Rawls, MD, MS. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1301–1313.
PURPOSE OF REVIEW
Parkinson disease (PD) is a progressive neurodegenerative disorder that is often difficult to manage with medications alone. This article reviews the current therapeutic surgical interventions for PD, patient selection criteria, timing of patient referral to surgical services, procedure overview, and future directions.
Adaptive, or closed-loop, deep brain stimulation is a promising therapy that can detect ongoing circuit changes and deliver appropriate stimulation based on the patient’s dominant symptom and level of dopaminergic medication.
Patients with PD can benefit from surgical interventions that can be added to their medication regimen. These patients should be referred to comprehensive centers that offer complete multidisciplinary screening evaluation to ensure appropriate patient selection and intervention selection. With the appropriate surgical intervention and continued management from their care team, patients with PD can maximize their quality of life.
- Surgical interventions do not slow down, stop, or reverse disease progression but are used to manage the symptoms associated with Parkinson disease.
- The three indications for deep brain stimulation surgery for the treatment of Parkinson disease include troublesome dyskinesias, frequent dosing because of troublesome off time, and medication-resistant tremor.
- Parkinson disease symptoms that are responsive to levodopa can be improved with deep brain stimulation; however, an exception to this is resting tremor, which may not be levodopa responsive but can still improve with deep brain stimulation.
- Disadvantages of deep brain stimulation include risks associated with brain surgery, hardware failure, infection risks, and concerns about patients with significant cognitive impairment.
- Deep brain stimulation can be performed on both sides of the brain and is adjustable over time.
- Commercial deep brain stimulation systems provide continuous stimulation without sensing brain signals for feedback (ie, open loop). There is ongoing research on deep brain stimulation systems that sense brain signals for feedback (ie, closed loop).
- MRI-guided focused ultrasound may be considered when there are restrictions to deep brain stimulation or other reasons that prohibit brain surgery.
- MRI-guided focused ultrasound uses multiple ultrasound beams that converge on a brain target to create an irreversible lesion.
- An advantage of MRI-guided focused ultrasound is that no foreign bodies are present in the patient following surgery. Disadvantages include that the US Food and Drug Administration has only approved this treatment for one side of the brain, and it is not adjustable.
- During stereotactic radiosurgery, multiple beams of radiation converge on the brain target to create an irreversible lesion.
- An advantage of stereotactic radiosurgery is that no foreign bodies are present in the patient following surgery. Disadvantages include that the US Food and Drug Administration has only approved this treatment for one side of the brain, it is not adjustable, and there is potential radiation risk.
- The levodopa/carbidopa intestinal gel infusion system provides levodopa infusion through a percutaneous endoscopic gastrojejunostomy, providing continuous levels throughout the day.
- The levodopa/carbidopa intestinal gel infusion system may not be appropriate for patients with poor response to levodopa or who have difficulty handling the infusion pump.
- Typically, the levodopa/carbidopa intestinal gel infusion pump is on during the day and is shut off at night.
- Advantages of the levodopa/carbidopa intestinal gel infusion system include that the pump can be disconnected when not in use and can be used in patients with significant cognitive impairment. Disadvantages include risks associated with percutaneous endoscopic gastrojejunostomy tube placement and maintenance.
ARTICLE 4: DIAGNOSIS AND TREATMENT OF COGNITIVE AND NEUROPSYCHIATRIC SYMPTOMS IN PARKINSON DISEASE AND DEMENTIA WITH LEWY BODIES
Daniel Weintraub, MD; David Irwin, MD. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1314–1332.
PURPOSE OF REVIEW
This article summarizes the underlying biology and current diagnostic and treatment strategies for the cognitive and neuropsychiatric features of Parkinson disease (PD) and dementia with Lewy bodies (DLB).
Cognitive impairment and neuropsychiatric symptoms have been increasingly recognized in PD and DLB, leading to improved diagnosis and treatment strategies. While PD is most associated with and diagnosed by the presence of motor symptoms, nonmotor symptoms can often be the most debilitating for patients. Neuropsychiatric symptoms are highly prevalent nonmotor features and include cognitive impairment, depression, anxiety, psychosis, impulse control disorders, and apathy. Neuropsychiatric symptoms can be difficult to recognize and diagnose in patients with PD, in part because of comorbidity and symptom overlap with core PD features. Treatment strategies are a combination of pharmacologic and nonpharmacologic interventions used in the general population and those specific to PD. DLB is a clinical dementia syndrome, often with similar cognitive, behavioral, autonomic, and motor features as PD. Moreover, DLB has shared underlying pathophysiology with PD, as both are associated with postmortem findings of α-synuclein neuropathology at autopsy and have shared genetic risk and prodromal symptoms. DLB is clinically differentiated from PD by the presenting features of cognitive impairment in DLB, compared with the variable onset of cognitive impairment occurring 1 year or more after established motor onset in PD. Thus, diagnosis and treatment of cognitive impairment and neuropsychiatric symptoms in DLB are similar to that of PD and have important implications for maintaining patient independence and providing support for caregivers because motor, cognitive, and neuropsychiatric symptoms have an additive effect on patient functional disability.
A careful history and physical examination are often needed to accurately diagnose and treat the heterogeneous cognitive and behavioral symptoms of PD and DLB. Accurate diagnosis and treatment of neuropsychiatric symptoms and cognitive impairment in PD and DLB are important, as these are a considerable source of patient disability and caregiver burden.
- Both Parkinson disease and dementia with Lewy bodies are classified as Lewy body disorders because of the shared underlying α-synuclein neuropathology.
- Parkinson disease dementia and dementia with Lewy bodies are differentiated from each other by the timing of the onset of cognitive impairment and dementia; in dementia with Lewy bodies, dementia is an early presenting feature compared with Parkinson disease, where cognitive impairment is variable and dementia occurs at least 1 year after the onset of motor symptoms.
- The majority of patients with Parkinson disease, especially those who are older and with long-standing disease, develop significant cognitive impairment.
- Patients with Parkinson disease can experience impairments in any of the major cognitive domains, even at the stage of mild cognitive impairment.
- Choice of Parkinson disease medication at disease onset does not appear to impact long-term cognitive course, but use of medications with significant anticholinergic properties may be associated with worse long-term cognitive outcomes.
- For Parkinson disease dementia, cholinesterase inhibitors are of modest benefit, and there is no clear benefit for memantine. For Parkinson disease–mild cognitive impairment, no medication has been shown to be efficacious.
- Management of comorbid medical conditions associated with cognitive impairment in Parkinson disease may lead to improvement in cognitive abilities.
- Accurately diagnosing depression in Parkinson disease can be complicated because of symptom overlap between depression symptoms, apathy, and core Parkinson disease symptoms.
- A range of antidepressants and Parkinson disease medications have been shown to be efficacious for the treatment of depression in Parkinson disease.
- There is increasing evidence for the efficacy of psychotherapy for depression and anxiety in Parkinson disease.
- Symptoms occurring as part of nonmotor fluctuations are a common presentation of significant anxiety, even panic attacks, in Parkinson disease.
- There have been no efficacy pharmacologic randomized clinical trials for anxiety disorders in Parkinson disease, but in clinical practice, antidepressants and sometimes benzodiazepines are used.
- It is now recognized that hallucinations in a range of sensory domains, not just visual hallucinations, can occur in Parkinson disease.
- Management of psychosis in Parkinson disease includes a mix of trying to lessen dopamine replacement therapy exposure and judicious use of antipsychotic medication.
- Antipsychotic use in patients with Parkinson disease may be associated with an increased risk of mortality and morbidity, as has been reported for Alzheimer disease.
- Screening for impulsive-compulsive disorders should include the range of impulse control disorders and related behaviors reported to occur in Parkinson disease, with attention to any comorbid disorders.
- Management of impulse control disorders and related behaviors involves a mix of decreasing dopamine replacement therapy, particularly dopamine agonists, psychopharmacology, and psychotherapy.
- Although evidence from randomized clinical trials is limited, dopamine agonists, cholinesterase inhibitors, and stimulants can be used in the management of apathy in Parkinson disease.
- Overall, deep brain stimulation surgery is associated with an increase in apathy symptoms postoperatively.
- Neuropsychiatric symptoms are core features of dementia with Lewy bodies. These include well-formed spontaneous and recurrent visual hallucinations and cognitive fluctuations. Depression, anxiety, and apathy are also common features.
- The presence of one or more pathogenic mutations in the glucocerebrosidase A gene, known to cause autosomal recessive Gaucher disease, is an important genetic risk factor for Parkinson disease and dementia with Lewy bodies.
- Rapid eye movement (REM) sleep behavior disorder is highly predictive of underlying α-synuclein pathology and eventual clinical conversion to Parkinson disease or dementia with Lewy bodies.
- Patients fulfilling criteria for probable dementia with Lewy bodies are highly likely to have underlying α-synuclein pathology, but many patients with clinical Alzheimer disease are found to also have varying amounts of α-synuclein pathology in the brain.
- Up to 50% of all Lewy body disorders (ie, Parkinson disease, Parkinson disease mild cognitive impairment, Parkinson disease dementia, and dementia with Lewy bodies) have sufficient plaques and tangles in the brain postmortem for a second neuropathologic diagnosis of Alzheimer disease. These patients with mixed pathology have a worse prognosis and unique clinical features.
- There are associations of sex and risk for Lewy body disorders, with greater frequency of men with α-synuclein pathology.
- The clinical diagnosis of dementia with Lewy bodies often takes several years to establish in part because of the lack of accurate diagnostic tests specific to cortical α-synuclein and the need to detect progressive cognitive impairment for diagnosis. Efforts to increase accessibility of assessment tools for the unique clinical neuropsychiatric symptoms can help improve diagnosis and treatment of dementia with Lewy bodies.
- Core clinical features of dementia in dementia with Lewy bodies are attention, executive, and visuospatial dysfunction, but episodic memory and language difficulties are not uncommon and have been linked to Alzheimer disease co-pathology.
- Cognitive fluctuations are core neuropsychiatric symptoms of dementia with Lewy bodies and can range from periodic confusion and disorganized speech to more prolonged episodes of confusion and depressed consciousness as well as excessive daytime fatigue. Detection and treatment of cognitive fluctuations can be aided by standardized caregiver questionnaires.
- There is an urgent need for therapeutic trials to guide treatment decisions in dementia with Lewy bodies.
- Treatment choices in dementia with Lewy bodies need to be individualized to patient and medical comorbidities. The heterogeneous cognitive, motor, and autonomic symptoms of dementia with Lewy bodies often require careful selection and titration of medications since many symptomatic choices have potentially competing mechanisms of action. Careful titration to the lowest effective dose is often a beneficial strategy.
- Data for pharmacologic and nonpharmacologic management of dementia with Lewy bodies are largely restricted to small open-labeled trials and meta-analyses. There are considerable data and general consensus among experts for the use of cholinesterase inhibitors as first-line treatment for cognitive impairment and fluctuations in dementia with Lewy bodies.
- Visual hallucinations in patients with dementia with Lewy bodies are often well-formed objects such as people, animals, or objects. Patients initially have good insight but progressively these can cause anxiety or agitation.
- It is important to first rule out delirium or other medical etiologies for visual hallucinations and remove or lower potentially exacerbating medications, such as dopaminergic therapies.
- The data on effective pharmacotherapy for visual hallucinations in dementia with Lewy bodies are limited. When problematic, careful use of low-dose second-generation neuroleptics may be helpful, but it is important to consider patient age and medical comorbidities. It is also important to first rule out delirium or other medical etiologies and remove or lower potentially exacerbating medications such as dopaminergic therapies.
ARTICLE 5: DIAGNOSIS AND TREATMENT OF ESSENTIAL TREMOR
Aparna Wagle Shukla, MD. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1333–1349.
PURPOSE OF REVIEW
Essential tremor is a chronic, progressive syndrome that primarily presents with an action tremor involving the arms and hands. This article reviews the history and physical examination features pertinent for diagnosis, differential diagnoses, and treatments and approaches for optimal control of symptoms.
Essential tremor is a syndrome with symptoms extending beyond tremor to involve disturbances in gait, speech, cognition, and mood. Although the new guidelines on the definition and biaxial classification scheme have provided clarity, some tremor experts have critiqued the recently coined term essential tremor plus. For treatment, new orthotic devices and peripheral stimulation devices are now available in addition to pharmacologic and surgical options.
Essential tremor has a rich clinical phenomenology with many subtleties and nuances. A detailed history with open-ended questions and focused questions encompassing medical history, social history, and family history is key for establishing the diagnosis. The presence of bilateral action tremor for 3 years and absence of isolated head and voice tremor and absence of task- and position-dependent tremor are necessary for diagnosis. Dystonic tremor, Parkinson disease tremor, physiologic tremor, and drug-induced tremor are common differential diagnoses. Differentiating these tremor disorders from essential tremor based on phenomenology and physical examination alone could be challenging; thus, clinicians should seek additional clues from a detailed history. Treatment could begin with noninvasive and nonpharmacologic therapies, especially in mild cases. As the severity increases, they can advance stepwise to include pharmacotherapies and surgical interventions. With the growing recognition that essential tremor is not a monosymptomatic disorder, management should involve a multidisciplinary team. Furthermore, treatment selection should be based on shared decision making between patients and providers that gives due consideration to severity of symptoms, level of functional disability, impact on social interactions, patient preferences, and patient expectations.
- The involuntary movements of essential tremor are both rhythmic and oscillatory.
- Tremor syndrome classification is biaxial, first based on clinical phenotyping and second based on underlying etiologies.
- Essential tremor is among the most prevalent movement disorders.
- Isolated tremor syndrome of bilateral upper limb action tremor present for at least 3 years is a requirement for the diagnosis of essential tremor.
- Patients with early-onset essential tremor commonly report at least one affected first-degree family member.
- Essential tremor is a syndrome with symptoms in many patients extending beyond tremor to involve disturbances in gait, speech, mood, and cognition.
- Essential tremor with a resting component or accompanied by soft signs of dystonic posturing or parkinsonism is labeled as essential tremor plus; currently, no evidence has been found that essential tremor plus is biologically distinct from essential tremor.
- Dystonic head tremor commonly affects women in their fifth decade and includes headaches, neck pain, posturing, and isolated head tremor.
- Isolated head tremor, voice tremor, and task- or position-specific tremor should not be diagnosed as essential tremor.
- Unlike essential tremor, dystonic head tremor often persists when the patient is examined while lying down.
- The tremor in dystonia may be neither rhythmic nor oscillatory.
- Arm tremor in dystonia is frequently unilateral and asymmetric.
- Unlike essential tremor, dystonic arm tremor may not reveal a clear axis during the spiral-drawing task.
- Based on physical examination alone, dystonic tremor may not be distinguishable from essential tremor; history must be given consideration.
- Unlike essential tremor, resting tremor in Parkinson disease increases in amplitude with walking and mental calculation and is generally asymmetric.
- Unlike essential tremor, arm tremor in Parkinson disease reveals a reemergent quality (a tremor that occurs after a finite latency period from the time the patient assumes a horizontal posture of the arm to the onset of the wrist and/or finger tremor).
- In contrast to essential tremor, the jaw tremor of Parkinson disease is more often noted when the patient’s mouth is closed and relaxed rather than while the patient is speaking.
- Head tremor is not a feature of enhanced physiologic tremor or drug-induced action tremor.
- Holmes tremor has resting, postural, and kinetic components.
- Fragile X-associated tremor/ataxia syndrome has a prominent intentional component.
- Wilson disease has prominent wing-beating postural tremor.
- Functional tremor is abrupt in onset and distractible, suggestible, and entrainable.
- Management of essential tremor requires a multidisciplinary team, and treatment selection requires shared decision making between patients and providers.
- Adaptive tools, orthotic devices, limb cooling, and peripheral stimulation devices are useful nonpharmacologic therapies for essential tremor.
- If the tremor is severity does not reduce despite multiple medication trials, surgical intervention may be warranted.
ARTICLE 6: MULTIPLE SYSTEM ATROPHY
Daniel O. Claassen, MD, MS, FAAN. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1350–1363.
PURPOSE OF REVIEW
Patients with multiple system atrophy (MSA) can present with diverse clinical manifestations, and the clinical care required is complex and requires a thoughtful approach to emerging symptoms and treatment decisions.
Even though it is a rare disease, MSA is often encountered in clinical practice. New developments in biofluid biomarkers and diagnostic assessments offer potential for earlier and more accurate diagnosis. This article describes recent findings, such as the use of skin biopsies, neuroimaging, and novel treatment concepts (eg, central noradrenergic augmentation).
MSA is a complex disease. This article provides a summary of treatment options for diverse symptoms that include autonomic, sleep, mood, and motor manifestations of the disease to help clinicians care for patients with MSA. Providing comprehensive care for patients with MSA requires an understanding of the diverse symptomatology that patients develop over time and should include an interdisciplinary team.
- Although multiple system atrophy (MSA) has been designated as MSA with predominant parkinsonism or MSA with predominant cerebellar ataxia, it is more common to see an overlap of symptoms that make this distinction difficult.
- The most common prodromal symptoms for MSA include rapid eye movement (REM) sleep behavior disorder and autonomic failure.
- Patients with pure autonomic failure have a high likelihood of progressing to a central α-synuclein disease; those who progress to MSA tend to be younger and have intact smell and an increase in heart rate after 3 minutes of standing up from a supine position.
- A reduction of systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg within 3 minutes of standing without compensatory heart rate increase is diagnostic of orthostatic hypotension.
- Elevating the head of the bed during the night should be encouraged in the management of supine hypertension in patients with MSA.
- Early integration of physical therapy and gait safety is key in managing MSA gait symptoms.
- Identifying pain symptoms is important in maintaining the quality of life of patients with MSA.
- Clinicians can educate local counselors or social workers about the nature of MSA to help establish the framework and goals for interactions.
- The use of activity of daily living screening tools for patients, such as the Unified Multiple System Atrophy Rating Scale Part 1, can help direct care of patients with MSA.
ARTICLE 7: PROGRESSIVE SUPRANUCLEAR PALSY AND CORTICOBASAL SYNDROME
Alexander Pantelyat, MD, FAAN. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1364–1378.
PURPOSE OF REVIEW
The differential diagnosis of parkinsonism (tremor, rigidity, bradykinesia, and gait difficulty/postural instability) is broad and includes two neurodegenerative conditions that exist on a clinicopathologic spectrum: progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Early in their clinical course, PSP and CBS may be difficult to distinguish from Parkinson disease and several other illnesses, but it is crucial to do so because of implications for management and prognosis.
Early accurate diagnosis of PSP and CBS remains a challenge because of heterogeneity in presenting symptoms and high frequency of coexisting pathologies (especially Alzheimer disease and vascular disease). It is increasingly recognized that patients with PSP, CBS, and other parkinsonian disorders require multidisciplinary care for optimal outcomes. With the recent proliferation of biomarker studies and therapeutic trials for tauopathies, there is growing hope that better treatments for PSP and CBS are on the horizon.
Although PSP and CBS currently lack disease-modifying therapies, it is important to diagnose them as early as possible so that the patient can benefit from the many available symptomatic therapies, support groups, and a growing number of clinical trials.
- The pathologic hallmark of progressive supranuclear palsy is the presence of tau protein isoforms with four microtubule-binding repeats (4-repeat tau), in astrocytic tufts (most specific for progressive supranuclear palsy), oligodendrocytic coils, and neurofibrillary tangles (least specific).
- It is important to perform genetic testing in patients with early age at symptom onset or a clear family history of atypical parkinsonism. Among genetic mimics of progressive supranuclear palsy, Niemann-Pick disease type C stands out, as it is a treatable condition.
- Progressive supranuclear palsy–Richardson syndrome (classic progressive supranuclear palsy) refers to akinetic-rigid parkinsonism with early falls and vertical eye movement impairment.
- Current clinical diagnostic criteria for progressive supranuclear palsy include levels of diagnostic certainty that offer trade-offs between specificity and sensitivity.
- Optokinetic nystagmus testing can be helpful in assessing saccades if gross saccade testing is equivocal.
- Progressive supranuclear palsy–parkinsonism is the second most common progressive supranuclear palsy variant and can be difficult to distinguish from Parkinson disease for several years from symptom onset.
- The parkinsonism in progressive supranuclear palsy–parkinsonism can be tremor-predominant or akinetic-rigid and may have a levodopa response, although typically without motor fluctuations or dyskinesias.
- Frontal-executive cognitive impairment is an important feature of both progressive supranuclear palsy and corticobasal syndrome.
- Key differential diagnosis considerations for progressive supranuclear palsy include Parkinson disease, other degenerative parkinsonian disorders (such as dementia with Lewy bodies and multiple system atrophy), normal pressure hydrocephalus, and vascular parkinsonism.
- The easily measured ratio of midsagittal midbrain to pontine base distances on T1-weighted MRI of less than 0.5 is highly sensitive and specific for progressive supranuclear palsy–Richardson syndrome but not other progressive supranuclear palsy variants.
- Corticobasal syndrome refers to the patient’s clinical presentation and typically includes asymmetric presentation of limb rigidity, akinesia, dystonia, myoclonus, and apraxia. Corticobasal degeneration is the term referring to specific 4-repeat tau pathology on brain autopsy.
- Corticobasal degeneration is most specifically characterized by astrocytic plaques, whereas progressive supranuclear palsy has tufted astrocytes.
- Corticobasal degeneration pathology accounts for only about 50% of corticobasal syndrome cases. The remainder of corticobasal syndrome cases are due to progressive supranuclear palsy, Alzheimer disease, and rarely other pathologies.
- Although it is a classic sign, alien limb phenomenon occurs in only about 20% of patients with autopsy-confirmed corticobasal degeneration.
- When completing a levodopa trial in progressive supranuclear palsy or corticobasal syndrome, maintain maximum tolerated levodopa dose for at least 1 month before gradual tapering.
- Dopaminergic medications other than levodopa are best avoided in progressive supranuclear palsy and corticobasal syndrome because of side effects and lack of efficacy.
- Anticholinergic medications should be avoided in progressive supranuclear palsy and corticobasal syndrome whenever possible because of the risk of worsening cognitive impairment.
- Pseudobulbar affect is a symptom of both progressive supranuclear palsy and corticobasal syndrome and may improve with selective serotonin reuptake inhibitors or dextromethorphan/quinidine.
- Depression and anxiety are common in progressive supranuclear palsy and corticobasal syndrome; selective serotonin reuptake inhibitors can be effective at standard doses.
- Modafinil or methylphenidate may be helpful for apathy in progressive supranuclear palsy and corticobasal syndrome.
- Botulinum toxin injections can help a range of symptoms in progressive supranuclear palsy and corticobasal syndrome, including sialorrhea, cervical and limb dystonia/spasticity, muscle pain, and eyelid opening apraxia/blepharospasm.
- Rehabilitation plays a key role in improving and maintaining function in progressive supranuclear palsy and corticobasal syndrome and should be maintained throughout the entire disease course.
- Physical therapy targets gait and balance rehabilitation and fall prevention in progressive supranuclear palsy and corticobasal syndrome.
- Occupational therapy targets upper extremity function, range of motion, and adaptive device use in progressive supranuclear palsy and corticobasal syndrome.
- Speech/swallow therapy targets dysarthria, aphasia, and dysphagia in progressive supranuclear palsy and corticobasal syndrome.
- Periodic swallow evaluations help assess aspiration risk and guide dietary modifications for liquids and solids.
- The number of clinical trials for progressive supranuclear palsy and corticobasal syndrome is growing, and it is important to refer patients for trial screening as early as possible.
ARTICLE 8: CHOREA
Erin Furr Stimming, MD, FAAN; Danny Bega, MD. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1379–1408.
PURPOSE OF REVIEW
This article provides an overview of the diagnostic and therapeutic approach to a patient with chorea. The phenomenology of chorea is described in addition to other common hyperkinetic movements that may be mistaken for or coexist with chorea. Chorea can be acquired or hereditary. Key historical and clinical features that can aid in determining the etiology are reviewed, and pharmacologic and nonpharmacologic treatment strategies are discussed.
Clinical investigations are under way to target transcription and translation of the mutant huntingtin protein as a potential disease-modifying strategy in Huntington disease (HD). Additional heritable factors have been revealed through genome-wide association studies. Symptom-focused treatments for HD are are being studied, including a third vesicular monoamine transporter-2 (VMAT2) inhibitor for chorea attenuation and drugs to target irritability and cognitive impairment. Increased availability of genetic testing has led to increased awareness of HD mimics (eg, C9orf72 and IgLON5).
Chorea is a relatively common hyperkinetic disorder with a broad differential. The first step in the approach to a patient with chorea is accurately defining the phenomenology. Once it has been determined that the patient has chorea, the investigation into determining an etiology can begin. Factors such as age of onset, time course, family history, unique clinical features, and imaging and laboratory findings can guide the diagnosis. Treatments for most causes of chorea are purely symptomatic, although it is important to recognize causes that are reversible or have disease-modifying interventions.
- Chorea refers to random, irregular, purposeless movements that flow from one body part to the next.
- Chorea is generalized in many patients; however, its localized distribution may act as an important diagnostic factor to determine the underlying etiology. For example, forehead involvement is more common in Huntington disease. Orobuccolingual chorea is more common in tardive syndromes.
- Because the differential diagnosis for chorea is broad, it is generally helpful to begin by categorizing chorea as (1) inherited versus acquired and (2) childhood onset versus adult onset.
- Clues to differentiate inherited choreas from acquired choreas include the timeline (acute, subacute, or chronic [>1 year]) and course (static, paroxysmal, or progressive).
- Huntington disease is the most common cause of adult-onset hereditary chorea. It is imperative that genetic counseling occur before testing.
- Huntington disease mimics or phenocopies include several inherited rare degenerative conditions and may be associated with the triad of chorea, dementia, and behavioral disturbances.
- Pathogenic variants in ATN1 dentatorubral pallidoluysian atrophy are associated with characteristic MRI changes in the dentate, red nucleus, and pallidum.
- Pathogenic variants in C9orf72 can mimic Huntington disease, but variable expression may also include amyotrophic lateral sclerosis and frontotemporal dementia.
- Pathogenic variants in VPS13A cause chorea-acanthocytosis, with characteristic orobuccolingual chorea and acanthocytes on blood smear. McLeod syndrome is an X-linked form.
- Chorea can result from abnormal mineral accumulation in the basal ganglia. This includes iron (neurodegeneration with brain iron accumulation), calcium (Fahr disease), and copper (Wilson disease), each of which may have corresponding MRI abnormalities.
- Mutations in ADCY5 are associated with childhood hypotonia. The chorea that may develop worsens with sleep deprivation.
- Paroxysmal disorders of chorea have characteristic triggers. Paroxysmal nonkinesigenic dyskinesia is triggered by stress, extremes of temperature, alcohol, or excitement. Paroxysmal kinesigenic dyskinesia episodes are shorter and more frequent and triggered by movement.
- Sydenham chorea is the most common cause of chorea in childhood.
- Antiphospholipid antibodies are associated with systemic lupus erythematosus, hypercoagulability, and chorea.
- IgLON5 is an antibody that has been discovered recently in association with parasomnias but can be associated with cognitive impairment, gaze palsies, and chorea.
- Structural or vascular lesions should be considered in cases of focal or hemibody chorea.
- Dopaminergic medications and antidopaminergic medications can cause choreiform movements. Careful medication history and timeline of exposure are important.
- Hyperglycemia is a common metabolic cause of acute-onset chorea associated with T1 signal change in the contralateral putamen on MRI.
- It is important to determine whether chorea is troublesome or bothersome before initiating a medication. Anosognosia is not uncommon, especially in Huntington disease; therefore, collecting input from the patient and their care partner is essential.
- Vesicular monoamine transporter-2 (VMAT2) inhibitors are the only class of medications currently approved by the US Food and Drug Administration for the treatment of tardive dyskinesia and/or chorea associated with Huntington disease.
ARTICLE 9: NEURODEGENERATIVE CEREBELLAR ATAXIA
Liana S. Rosenthal, MD, PhD. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1409–1434.
PURPOSE OF REVIEW
Neurodegenerative cerebellar ataxia is a diverse collection of diseases that are unified by gait and balance abnormalities, appendicular incoordination, and abnormalities of eye movement and speech. The differential diagnosis is broad, ranging from paraneoplastic syndromes that progress quite rapidly to unidentified genetic disorders that progress slowly over the course of decades. This article highlights the diagnostic process, including the differential diagnosis, as well as treatment approaches and symptomatic management. The pillars of treatment are physical, occupational, and speech therapy as well as counseling and discussions of disease prognosis, genetics, and reproductive choices. There are many ways to help patients with neurodegenerative cerebellar ataxia and improve their quality of life.
Recent years have seen significant improvements in genetic testing, with reductions in cost of both Sanger sequencing and whole exome sequencing and increasing availability of the latter. These improvements increase clinicians’ ability to identify the etiology of neurodegenerative cerebellar ataxia and suggest future treatments. Although no medication has been approved by the US Food and Drug Administration (FDA) for treatment of cerebellar ataxia, research and clinical trials for these diseases are increasing.
Neurodegenerative cerebellar ataxia is characterized by dysarthria, dysmetria, oculomotor abnormalities, and ataxic gait. It has a broad differential diagnosis, and numerous options exist for managing symptoms. Although no medications have been approved specifically for cerebellar ataxia, treatment options are available to improve patients’ quality of life.
- Ataxia can be classified into three broad types: (1) sensory ataxia due to neuropathy in the feet; (2) vestibular ataxia due to dysfunction of the semicircular canals, otolith organs, or both; and (3) cerebellar ataxia due to dysfunction of the cerebellum.
- The vermis is responsible for axial function, while the paravermis is responsible primarily for limb function.
- Patients with cerebellar ataxia describe falls and clumsiness but often describe the initial symptoms as being difficulty maintaining balance on uneven ground, when going up or (primarily) down stairs, or when running.
- Examination of individuals with cerebellar ataxia usually reveals a wide-based gait with some titubation observed, specifically on turns.
- Speech, swallowing, and eye movement abnormalities are especially important for cerebellar localization, as these findings indicate that the lesion is above the spinal cord.
- Eye movement changes, specifically downbeat nystagmus, square-wave jerks, and hypermetric or hypometric saccades, are often the best way to localize the patient’s ataxia to the cerebellum.
- Individuals with cerebellar lesions often report difficulty meeting their target with their hands, while individuals with extrapyramidal lesions often report that their fingers will not do what their brain is asking.
- Individuals with cerebellar ataxia without extrapyramidal involvement often demonstrate pauses and clumsiness on finger tapping, hand opening and closing, and pronation and supination but do not have a decrementing bradykinesia.
- Individuals with what is known as cerebellar cognitive affective syndrome present with challenges in executive function, linguistic processing, and spatial cognition.
- Absence of cerebellar atrophy does not change the localization, as an overall normal-sized cerebellum may be observed even among individuals with significant cerebellar dysfunction. The presence of cerebellar atrophy, though, helps to confirm the localization.
- Testing for nongenetic and then genetic etiologies is an iterative process, circling back on each possibility to ensure that all reasonable and appropriate testing to identify the etiology has occurred.
- When evaluating the results of blood work, it is important to distinguish between those results that are outside of normative values and those results that are actually diagnostic for the cause of the cerebellar ataxia.
- For many of the genetically identified spinocerebellar ataxias, as well as other genetic diseases, in vitro fertilization with preimplantation genetic diagnosis allows for eradication of the genetic disease in the next generation.
- If genetic testing is not successful in identifying the etiology of cerebellar ataxia, the next step is to evaluate for other diagnostic possibilities.
- The most important principle in the treatment of neurodegenerative cerebellar ataxia is that although no disease-modifying therapy or even medications specifically approved to treat cerebellar ataxia are currently known, there is always something that can be done to improve the individual’s quality of life.
- Exercise has been shown to improve ataxia motor symptoms and is critical to maintain function for as long as possible.
- Swallowing difficulties may be treated by behavioral modifications or dietary changes, both of which have been shown to be effective.
- Several therapies for neurodegenerative cerebellar ataxias are in earlier stages of development, increasing the possibilities for new symptomatic or even disease-modifying therapies in the future.
ARTICLE 10: THE DYSTONIAS
Christopher D. Stephen, MB ChB, FRCP, SM. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1435–1475.
PURPOSE OF REVIEW
This article discusses the most recent findings regarding the diagnosis, classification, and management of genetic and idiopathic dystonia.
A new approach to classifying dystonia has been created with the aim to increase the recognition and diagnosis of dystonia. Molecular biology and genetic studies have identified several genes and biological pathways involved in dystonia.
Dystonia is a common movement disorder involving abnormal, often twisting, postures and is a challenging condition to diagnose. The pathophysiology of dystonia involves abnormalities in brain motor networks in the context of genetic factors. Dystonia has genetic, idiopathic, and acquired forms, with a wide phenotypic spectrum, and is a common feature in complex neurologic disorders. Dystonia can be isolated or combined with another movement disorder and may be focal, segmental, multifocal, or generalized in distribution, with some forms only occurring during the performance of specific tasks (task-specific dystonia). Dystonia is classified by clinical characteristics and presumed etiology. The management of dystonia involves accurate diagnosis, followed by treatment with botulinum toxin injections, oral medications, and surgical therapies (mainly deep brain stimulation), as well as pathogenesis-directed treatments, including the prospect of disease-modifying or gene therapies.
- The term dystonia can be used as both a clinical descriptor of an abnormal posture, frequently with a twisting, patterned quality and a group of diseases, where dystonia is the main clinical feature.
- The dystonias include idiopathic, genetic, acquired, and other causes. No reliable diagnostic test (outside of genetic testing) currently exists, as imaging and laboratory testing are typically normal in patients with dystonia.
- Clinical features of dystonia include influence by voluntary action, overflow/mirror dystonia, and a “null point.” Sensory tricks should be specifically inquired about and assessed on examination.
- Dystonia is classified based on clinical characteristics (age of onset, body distribution, temporal pattern, and associated clinical features) and etiology (underlying nervous system pathology or whether the condition is inherited, acquired, or idiopathic).
- Nomenclature of genetic dystonias involves referring to the movement disorder type (including if combined) and gene name, not DYT locus, using recently updated criteria.
- The diagnosis of dystonia is challenging. Common misdiagnoses occur in patients thought to have Parkinson disease, essential tremor, myoclonus, tics, functional (“psychogenic”) dystonia, headaches, and scoliosis.
- Despite increasing recognition, limited data exist on dystonia epidemiology. Given the common misdiagnoses, the prevalence of dystonia may be up to 1 in 1000 individuals. There are age, sex, racial, ethnic, and geographic variations.
- Adult-onset idiopathic focal/segmental dystonias are the most common dystonic conditions and infrequently generalize, although there may be progression over time. These include cervical, cranial, oromandibular, laryngeal, limb, and truncal dystonia.
- Many genetic forms of dystonia exist. Genetic isolated dystonias are mainly autosomal dominant.
- Autosomal recessive dystonia is much less common than autosomal dominant cases and should be suspected if there are multiple affected individuals within the same generation, but not in their parents, or parental consanguinity.
- Combined dystonias involve dystonia and other movement disorders, frequently parkinsonism or myoclonus. Considerable clinical and genetic heterogeneity exists.
- The paroxysmal dystonias/dyskinesias are rare disorders involving episodic hyperkinetic movements, including dyskinesia or dystonic movements. These are typically early-onset disorders arising in childhood or adolescence, occurring very rarely after age 18.
- The first step of management requires accurate diagnosis. If an idiopathic (generally late-onset) dystonia is suspected, further diagnostic workup is not typically necessary.
- Directed workup includes laboratory testing to rule out Wilson disease and neuroimaging followed by specific targeted testing, including genetic testing with concomitant genetic counseling.
- Treatment of dystonia depends on the diagnosis (idiopathic versus genetic) and whether potential pathogenesis-directed treatments are available. Symptomatic medical therapy often involves botulinum toxin injections, oral medications, and rehabilitation, with deep brain stimulation considered for treatment-refractory cases or conditions where good evidence of efficacy exists.
- Disorders for which pathogenesis-directed treatments are available include dopa-responsive dystonia, Wilson disease, the paroxysmal dyskinesias, and rare, complex metabolic dystonias. All young-onset cases should have a trial of levodopa to assess for dopa-responsive dystonia.
- The goal of symptomatic therapy for dystonia is to provide relief from abnormal movements/postures, associated pain and discomfort, contractures or other orthopedic complications of sustained abnormal postures, and medical comorbidities, including neuropsychiatric symptoms. This should be individualized for each patient.
- Treatment of drug-induced/tardive dystonia involves early diagnosis and discontinuation of the offending drug, discontinuation of anticholinergics, and specific antidyskinetic medications, with DBS considered in severe, refractory cases.
- Botulinum toxin injections form the cornerstone of focal dystonia treatment. Serotypes A and B are approved for treatment. Patients generally receive injections every 12 weeks, although many patients experience a shorter duration of effect. Patients rarely develop neutralizing antibodies, and this can be assessed with a “frontalis test.”
- Oral medications for dystonia treatment are generally considered in cases of generalized dystonia or more severe disease and are much better tolerated in younger patients. These mainly involve dopaminergic therapy, anticholinergics, baclofen, and benzodiazepines.
- The paroxysmal dystonias/dyskinesia have specific treatments: Paroxysmal kinesigenic dystonia/dyskinesia is treated with anti-seizure medications, (typically carbamazepine or oxcarbazepine); paroxysmal nonkinesigenic dystonia/dyskinesia is typically treated with low-dose benzodiazepines; and paroxysmal exercise/exertion-induced dystonia/dyskinesia is treated with ketogenic diet, L-carnitine supplementation, and triheptanoin.
- Noninvasive brain stimulation is a developing area of potential therapy for dystonia but has mainly been used for research purposes and includes transcranial magnetic stimulation and transcranial direct current stimulation.
- Surgical treatments of dystonia include intrathecal baclofen pumps, ablative lesioning, and deep brain stimulation.
- Focused ultrasound has evidence for efficacy for dystonia, although symptom recurrence is possible, requiring repeat lesioning. This is only approved for unilateral use.
- DBS has potential advantages over focused ultrasound, including a more favorable side effect profile, the potential for reversibility, and the ability to adjust the stimulation direction and field. The main stimulation site is the globus pallidus internus; however, efficacy has also been demonstrated in targeting the subthalamic nucleus and thalamus. Cerebellar stimulation is currently under investigation.
- Status dystonicus/dystonic storm is a medical emergency, fatal in 10%. Precipitants include infection, medication changes, or deep brain stimulation hardware failure. Management involves treating triggers and oral dystonia therapies followed by intensive care unit–level care and consideration of rescue deep brain stimulation.
ARTICLE 11: DIAGNOSING COMMON MOVEMENT DISORDERS IN CHILDREN
Jennifer A. O’Malley, MD, PhD. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1476–1519.
PURPOSE OF REVIEW
This article is designed to help the clinician identify the most common pediatric movement disorders and recognize benign versus pathologic movements in infancy and childhood, with a particular focus on treatable conditions and those that should not be missed.
As telehealth has become more prevalent as a means of providing health care services, the challenges of obtaining relevant examination findings during telehealth encounters for assessment of children with movement disorders have become evident.
Although many children who present with a chief complaint of “abnormal movements” are found to have a benign, self-resolving etiology, it is critical that neurologists accurately recognize benign versus pathologic movements in children to ensure appropriate diagnosis and intervention.
- Developmental control of voluntary movement begins at the head and neck and progresses to the trunk and then the extremities (rostrocaudal gradient).
- Coordinated movement involves the whole brain, not just the basal ganglia and motor cortices but also the brainstem, limbic system, cerebellum, frontal lobes, and nonmotor pathways.
- Voluntary movement involves an intricate balance of “stop and go” signaling, with dopamine playing the role of fine motor modulator.
- Understanding phases of movement (motor planning, initiation, and execution) can help to better identify abnormal movements.
- The clinician should ask the child about their movements: what, where, when, with whom, wax/wane, worsening, why (Why do you think you have these movements?) (What do you want help with?).
- The clinician should pay careful attention to developmental milestones and watch for signs of subtle delay when evaluating a child for movement disorders.
- The clinician should dig deep on family history; encourage parents to ask their families about their own childhood movements when evaluating a child presenting with a movement disorder.
- Understand both the manifestation and functional impact of movements in multiple environments when evaluating a child presenting with a movement disorder.
- Ask about and normalize worry to further explore the role of anxiety when evaluating a child presenting with a movement disorder.
- Understanding of developmental milestones is key to recognizing normal versus abnormal movements.
- Observation is an essential skill for the pediatric movement examination.
- Making the examination fun and using play to elicit movement patterns is key to an efficient and thorough movement examination in children.
- Tone is dynamic. Accurate and thorough understanding of tone demands examination in multiple states (at rest, with activity, while asleep).
- Many abnormal movements in children are benign and will resolve with development.
- Tics and stereotypies are the most common benign movement disorders in childhood.
- Benign motor stereotypies typically do not require intervention.
- Urge and suppressibility are key features of tics.
- Nonpharmacologic interventions for tics include comprehensive behavioral intervention for tics.
- Movement disorders in children can present with phenomenology similar to that in adults and may be categorized as chorea, dystonia, myoclonus, tremor, ataxia, spasticity, and parkinsonism.
- Unlike adults, children often present with a mixed movement disorder; thus, discerning the primary phenomenology can be challenging but remains the foundation of accurate and timely diagnosis and treatment.
- Sydenham chorea is a common cause of treatable acute-onset chorea in children. Early recognition and diagnosis allow for appropriate intervention with steroids for symptom management.
- Symptom severity in Sydenham chorea is highly variable, but children commonly present with complaints of new clumsiness (dropping items, falling), gait instability, irritability, poor coordination, and possible changes in speech and behavior.
- Sydenham chorea is a form of rheumatic disease; thus, screening and monitoring for associated cardiac involvement are imperative.
- Genetic causes for chorea should be considered in any child with new-onset subacute progressive chorea, especially if accompanied by other neurologic or psychiatric features.
- For the child with spasticity and dystonia, surgical intervention must be considered carefully, as certain interventions for spasticity (in particular, selective dorsal rhizotomy) may improve the spasticity but “unmask” concurrent dystonia, resulting in worsened motor function.
- Surgical candidates should be evaluated by a multidisciplinary review board including specialists in neurology, neurosurgery, and physical, occupational, and speech therapy, as well as undergo a thorough psychosocial evaluation.
- Surgical intervention with pallidal deep brain stimulation should not be delayed for children with medication-refractory progressive dystonia.
- It is always prudent to trial levodopa for any child with dystonia to rule out a treatable dopa-responsive dystonia.
- Examples of benign physiologic myoclonus include hiccups, exercise- or anxiety-induced myoclonus, benign neonatal sleep myoclonus, or hypnic jerks in older children.
- The most common causes of tremor in children are the primary tremors: developmental tremor, enhanced physiologic tremor, and essential tremor.
- The clinician should obtain a thorough family history and examination of accompanying family members at the time of neurologic examination for tremor.
- Toxic ingestion is at the top of the differential diagnosis for acute ataxia.
- Clinical distinction between spasticity, dystonia, and rigidity is essential for accurate diagnosis and appropriate treatment of the hypertonic child.
- Although spastic cerebral palsy is the most common type, many children with cerebral palsy present with a mixed movement disorder.
- Key principles regarding the diagnosis of cerebral palsy are as follows: (1) Cerebral palsy is a clinical description and not an etiology. (2) Cerebral palsy is a permanent disability. (3) Cerebral palsy is a nonprogressive brain process, but the physical manifestations of the disorder are not necessarily static.
- Botulinum toxin injections for focal spasticity are approved by the US Food and Drug Administration for children 2 years old and older and may be used in isolation or in conjunction with oral medications.
- Recognition of spasticity and distinction from dystonia and rigidity is particularly important when considering possible etiologies as well as appropriate therapeutic interventions for cerebral palsy.
- Some surgical procedures targeting spasticity, such as selective dorsal rhizotomy, may actually worsen a patient’s function if their dystonia is mistaken for spasticity.
- Parkinsonism in infants may be difficult to identify as such and should be considered for any infant with hypotonia and reduced movement of undetermined etiology.
- Early and accurate diagnosis of functional movement disorders avoids excessive medical testing and treatment and delayed diagnosis and enables implementation of appropriate interventions.
- Diurnal fluctuation of symptoms may point to an underlying neurometabolic disorder.
- Potentially life-threatening drug-induced movement disorders include acute dystonic reaction, neuroleptic malignant syndrome, and serotonin syndrome.
- It is prudent to consider referral for pediatric deep brain stimulation for any child with medication-refractory dystonia, chorea, or tremor.
ARTICLE 12: PALLIATIVE CARE AND MOVEMENT DISORDERS
Maya Katz, MD. Continuum (Minneap Minn). October 2022; 28 (5 Movement Disorders):1520–1529.
PURPOSE OF REVIEW
This article reviews the role of palliative care in the treatment of patients with life-limiting neurodegenerative movement disorders.
Growing evidence indicates that palliative care significantly improves quality of life and symptom burden for people with Parkinson disease and other serious movement disorders, while reducing caregiver burnout. An emphasis on advance care planning guides goal-directed treatment recommendations. Serious illness communication skills are evidence-based methods of relaying bad medical news to patients and mapping out values and goals in a way that provides comfort, emphasizes patient autonomy, and builds coping and resiliency strategies.
Palliative care, when offered alongside primary medical and neurologic teams, provides an extra layer of support for people with serious illnesses. The goal of palliative care is to intensively treat total pain, which includes all of the physical, emotional, social, and spiritual distress caused by serious illness. Serious illness communication skills are key to providing empathic and goal-concordant care.
- Palliative care is specialized medical care for people with serious, life-limiting illness.
- Total pain is a key concept in palliative care that is defined as all of the physical, emotional, social, and spiritual distress caused by serious illness.
- The total symptom burden measured in Parkinson disease has been found to be similar to the total symptom burden reported in metastatic cancer and amyotrophic lateral sclerosis.
- Caregivers often experience serious adjustment reactions, burnout, chronic grief, and anticipatory grief.
- Growing evidence shows that palliative care significantly improves quality of life and symptom burden for people with Parkinson disease and other serious movement disorders, while reducing caregiver burnout and improving advance care planning.
- Palliative care is applicable at all stages of serious illness and in conjunction with other treatments that are focused on prolonging life.
- Palliative care serious illness communication skills are evidence-based teachable techniques that enable clinicians to break bad medical news and discuss advance care planning in a way that provides comfort, improves patient and caregiver coping, and guides treatment recommendations.
- The SPIKES protocol is a palliative care communication technique used when giving a serious illness diagnosis. SPIKES stands for: setting, perception, invitation, knowledge, emotions, and strategy.
- The REMAP protocol is a palliative care communication technique developed by VitalTalk that is used when there is significant worsening of the serious illness. REMAP stands for: reframe, expect emotion, map out, align, and plan.
- The high rates of dementia and communication difficulties that occur owing to neurodegenerative movement disorders makes discussing advance care planning early in the course of the illness critical.
- A documented advance care plan increases the likelihood of dying at home with hospice in a population of people with Parkinson disease, and movement disorders palliative care clinics have been shown to increase advance care planning.
- Requests for medical-aid-in-dying medications are typically a cry for help due to unbearable symptoms from a serious illness and are not usually disclosures of suicidal ideation.
- Palliative care considers clinicians to also be caregivers, with a high risk of caregiver burnout. Palliative care makes preventing clinician burnout a top priority by placing importance on developing a balanced lifestyle, building coping and resiliency skills, and developing systems-level improvements.
- The stigma surrounding the word “palliative” deters clinicians from recommending the treatment and deters patients/caregivers from accepting the care. Supportive care has been shown to be much better received by both clinicians and patients and caregivers.
- Palliative care emphasizes a holistic approach, patient autonomy, aggressive symptom management of total pain, concern for the family, and clinical teamwork to provide goal-concordant care that focuses on optimizing quality of life for people dealing with serious, life-limiting illness.