Describing Clinical Features of Movement Disorders for Effective Research Reporting

The many different types of movement disorders are each defined by their clinical features. The clinical features of a given group of disorders are sometimes referred to as phenomenology, semiology, or clinical phenotype. For both clinical management and research in movement disorders, a complete and precise characterization of these clinical features is essential. Good clinical descriptions provide essential data to support reports that involved advanced technologies, such as neuroimaging and genetics. However, good clinical descriptions alone can also provide valuable reports when they inform clinical practice or point to novel potential disease mechanisms. This viewpoint describes how these clinical features can be learned and then applied for effective research reports. We also further dissected how an enhanced approach to phenomenology can lead to successful reporting. There are limited opportunities to learn movement disorders during early phases of medical training such as medical school or residency, so most clinicians learn movement disorders during a dedicated fellowship that usually lasts at least a year. After learning the basics regarding common movement disorders, a good strategy for honing expertise is to learn about the less common problems "one case at a time". For this strategy, whenever an unusual case is encountered, it can be useful to invest time exploring other resources to learn more about it. Anchoring the larger database of information in the literature to a case from personal experience makes the disorder easier to remember. Beyond direct clinical experience, there are numerous additional resources for learning more. The first resource is the published literature. There are numerous texts and reviews that span all movement disorders. There are additional texts and reviews that focus on individual movement disorders. In fact, there are so many different publications that it can be difficult to know which ones to select, especially when information from different sources is not aligned. Consensus reports from the Movement Disorders journal and its sister journal Movement Disorders Clinical Practice are good resources because articles are peer-reviewed and usually written by multiple experts in the field. This strategy helps to resolve differences of opinion. These are often endorsed by the International Parkinson Disease and Movement Disorders Society (MDS), as well as other professional societies (Table 1). Also, the Movement Disorders journal is the first journal to adopt videos, thus creating a worldwide library of disorders that can be instrumental in guaranteeing a shared understanding of what features make a given movement disorder, beyond the limitation of written descriptions. Another resource for learning movement disorders involves meetings, either in person or via the internet (Video 1). For example, the MDS sponsors a yearly international meeting covering all types of movement disorders, as well as numerous smaller meetings that focus on needs of a particular topic or geographical area (www.movementdisorders.com). When a busy schedule does not permit attending meetings, there are numerous internet resources that may be accessed at a more convenient time. The MDS Roadmap provides an enormously valuable resource that is appropriate for all levels of expertise (www.movementdisorders.org/MDS/roadmap-overview). Beginners may use it to develop a basic knowledge of all movement disorders, and more advanced users fill gaps relating to limited experience with less common disorders. Learning movement disorders is a lifelong process, and it is probably impossible to know everything. Even the most advanced and experienced movement disorder experts occasionally encounter a patient with a problem that they have never seen before. When facing a new patient with a movement disorder, two different strategies can be used for evaluation. The first is the complete neurological evaluation, and the second is the hypothesis testing evaluation. The complete neurological evaluation is the traditional approach, with a complete history (chief complaint, detailed history of relevant associated problems, full medical and surgical history of unrelated problems, medicines list, social and family history) and a complete medical and neurological exam (mental state, cranial nerves, motor function, sensory function, coordination, and reflexes). This strategy is taught to medical students and residents, to be sure they learn the complete evaluation. It is very useful because it makes missing things unlikely. Movement disorders specialists often carry this strategy forward early in their careers. However, with more experience, the hypothesis testing evaluation can be more efficient, and it can save time in a busy clinical practice. With this strategy, knowledge of the chief complaint generates initial ideas regarding the potential causes. The hypothesis-testing approach then focuses the history on asking about features that confirm or refute these ideas, and the differential diagnosis becomes narrower. The exam further focusses specifically on looking for features that confirm or refute remaining items on the differential diagnosis list, and the list becomes even shorter. This approach can be more efficient, because it is not always necessary to collect a complete database of the history and exam to reach a diagnosis. The main limitation of this method is that it requires some experience to generate the initial differential diagnosis, and to know the most useful questions and examinations features to look for. When the hypothesis-testing approach fails to arrive at an answer, it is sometimes necessary to go back to do a more complete evaluation. Most movement disorder experts recommend a methodical approach for describing movement disorders that includes three sequential steps. The first step involves describing what the abnormal movements look like in terms of speed, frequency, repetitiveness, directions, body regions affected, and any associated abnormalities. This step can be done even by beginners and requires little expertise, other than knowing what features are most useful to describe. The second step involves considering which type of movement disorder best describes what is seen such as parkinsonism, tremor, ataxia, dystonia, chorea, myoclonus or others. Sometimes the best descriptors may include more than one type of movement disorder. Other disorders affecting movement,7 such as weakness or orthopedic limitations should also be described, not only because they influence the clinical picture but also because they can contribute to the third and final step: building a list of potential causes. The most common mistake is to skip the first step and jump directly to a judgment regarding the type of movement disorder or its diagnosis. This error should be avoided because it narrows the differential diagnosis. An example is an individual who demonstrates a stiff-appearing gait. This type of gait should not be described as "spastic", but rather as "stiff" with any additional features also noted. The reason is that "spastic" implies a corticospinal defect whereas a stiff-appearing gait can also reflect other motor disorders such as dystonia, parkinsonism, stiff-person syndrome, or even orthopedic problems. Another example might be repetitive jerking of a hand. While it might be tempting to immediately label it as "myoclonus", it is better to describe the jerks in more detail, including frequency, regularity, triggers, postural changes, and any accompanying features. The reason is that such jerking might be tics, dystonia, or even epilepsy. Perhaps the most common problem error in describing movement disorders relates to the term "ataxia". Many general neurologists use this term rather nonspecifically to refer to any poorly coordinated movement. However, poorly coordinated movements may have multiple reasons, eg, weakness or chorea. Most movement disorders experts prefer to reserve the term "ataxia" to describe a syndrome of dysmetria (abnormal distancing), dysrhythmia (abnormal single joint timing), dysdiadochokinesia (abnormal multi-joint timing), and dyssynergia (abnormal coordination). This syndrome is most often the result of cerebellar dysfunction, leading to common use of the term "cerebellar ataxia". However, this combination term should be avoided because ataxia may also arise from dysfunction of the cerebellar connections in the brainstem, the thalamus, and sometimes even the frontal cortex and other regions. Another term that can be a source of confusion is "apraxia", often used to describe difficulties in producing a movement in absence of clear sensory or motor causes. Examples include "gait apraxia" and "apraxia of speech".8 Such uses are too broad and don't adhere to formal definitions of apraxia as a disorder of the "gesture" with a cortical/cognitive origin. It is common to see movement disorders described according to a simple dichotomy, hypokinetic or hyperkinetic. Hypokinetic disorders include Parkinson's disease and related parkinsonian syndromes where there is a reduction in the frequency of movements and many movements are slowed. Hyperkinetic disorders are characterized by an increased frequency of movements and include chorea, dystonia, tics, tremor, and myoclonus. This dichotomy may provide a simple starting tool for teaching beginners, but it is often inadequate for more advanced practitioners in movement disorders for two main reasons. First, this dichotomy oversimplifies a far more complex reality. Parkinson's disease is the prototypical "hypokinetic" disorder, yet many individuals have tremor or other movements that are classified as "hyperkinetic", eg, levodopa-induced dyskinesias. Dystonia is classified as a hyperkinetic disorder, yet many movements are also slowed. Thus the division of hypokinetic and hyperkinetic is a bit overly simplistic for advanced practitioners in movement disorders. The other reason that the hypokinetic-hyperkinetic dichotomy is inadequate is that its origins aimed at describing disorders of the basal ganglia. The dichotomy is not suitable for cerebellar ataxias, where there often is a combination of hypokinetic and hyperkinetic movements to varying degrees, but the real problem is in the coordination of movement. The dichotomy also is hard to apply to disorders of the corticospinal pathways such as spastic paraparesis. Teaching how to successfully implement clinical description for scientific publication is not an easy task. Among the many factors, the process requires a combination of knowledge, experience and creativity. However, the process begins with astute observation. Good descriptions of clinical features and be exploited for research reporting in four main strategies, outlined below. This is probably the easiest scenario, because it is often useful to provide an accurate description of clinical features in the context of a rare disease that may not already be sufficiently described. An example of such a scenario is the description of freezing of gait in a child with NMDA receptor encephalitis.9 This condition is not uncommon in young female adults but it is less common in children, where it is less often paraneoplastic or complicated by behavioral problems. Movement disorders, chorea in particular, have been reported but never freezing of gait. Conversely, rare disorders that typically emerge during childhood may even more rarely emerge in late adulthood. Such reports are valuable to remind adult neurologists that they may be the first to encounter one of these disorders, some of which are treatable.10 Examples include Wilson's disease or dopa-responsive dystonia presenting after 40 years of age.11, 12 Educational case reports belong in this group, which may also be described as "learning one case at a time" as noted above. Generally, a report on a rare condition can highlight the main phenomenology and learning points or focus on particular aspects to aid clinical recognition, especially when combined with a literature review tabulating common features. An example is a case report of a young man with tremor and cognitive/behavioral changes linked to the AARS2 gene, where a literature review disclosed only 47 cases, most of whom presented with a movement disorder and cognitive/behavioral changes.13 Summarizing these reports aids future recognition of this very rare disorder. Accurate documentation (with video, electrophysiology or pathology) of a well-known manifestation can be valuable too, as showing the clinical features of "around the house" vertical eye movement defect or gelastic cataplexy in Niemann Pick Type C.14, 15 A rigorous observation might also lead to the description of a common feature not previously recognized, as happens with rare conditions not easily accessible unless working in a center with an invested interest. This was the case of the first case series of antecollis in patients with SCN1A mutations (Dravet syndrome),16 a clinical sign also reported to increase the diagnostic yield of the syndrome itself, eg, when compared to Lennox-Gastaut syndrome.17 A collaboration between subspecialties is very useful in this scenario, as for the case of epilepsy combined with movement disorders. Cohorts of children diagnosed with developmental and epileptic encephalopathies are noted to have a high frequency of movement disorders.18 Another example is the study of neuromuscular problems in patients with movement disorders, such as myasthenia gravis in dystonia19 or Parkinson's disease.20 The latter represent an example of unusual conditions because two relatively common conditions are found in the same individual. These reports can provide valuable lessons for treatment, eg, safety of botulinum neurotoxin injection in myasthenia gravis, a theoretical contraindication to agents blocking the neuromuscular junction.19 They can also shed light on pathophysiology, as in patients with congenital mirror movements and tremor, who contributed to the understanding of the role of the primary motor cortex in tremor propagation.21 The collaboration between different specialties can also expand outside neurology. An example is hepatic myelopathy, a rare and debated cause of spastic paraplegia in patients with liver failure.22 Lastly, when reporting on the usual presentation of unusual conditions, one can take the chance to review the literature on the topic and also highlight possible inconsistency or controversies. Here an example is a report on hemidystonia, which traditionally has been defined as "half" the body. However, what constitutes "half" has never been clearly defined, leading to variations in the use of this label.23 These reports provide valuable lessons for clinical practice as they highlight clinical concepts that might assist the diagnosis of conditions thought to be already known in their full manifestation. An example is tic-induced gait disturbance in patients with Tourette's Syndrome, a condition mimicking freezing of gait due to its episodic and sudden occurrence.24 Of note, when dealing with such cases it is advisable to replicate the finding, often collaborating with other groups who might have seen the same phenomenon. For example, freezing of gait caused or worsened by levodopa, a rare complication of Parkinson's disease, has been published in a case series of four cases collected in three international centers.25 There are numerous additional examples such as Parkinson's disease presenting with apparent hemiparesis, dystonia presenting with apparent spastic paraparesis, spinocerebellar ataxia presenting with focal dystonia, or Wilson's disease presenting with a persistent cough.26-28 Scientific or even informal discussions with colleagues is key in recognizing these opportunities. For example, the largest series of facial psychogenic movement disorders, an entity thought to be rare in the past, originated from the gathering of few colleagues during the faculty dinner of a medical conference: starting from two cases, a group representing seven centers was able to collect 61 in few months.29 This is probably the most difficult scenario, although it can be very rewarding because the resulting publications can be very useful. In the course of our clinical practice we're constantly exposed to phenomenology and over time, a curious and attentive researcher can notice interesting novel clinical signs worth being reported. For example, the finger tap is routinely performed dozens of times in a single day to assess appendicular bradykinesia in Parkinson's disease. Performing the task provides the observer with additional and overlooked information, as for example the height the patient's hand is held at, which tends to be very low and close to the body off levodopa and above the head on levodopa with dyskinesias.30 Once again, collaboration with other specialties or sub-specialties can be of assistance here. Can a motor focal seizure fulfill the diagnostic criteria for a movement disorder? We challenged a group of experts with videos of epileptic patients and found that this is the case in 29% of the patients.31 Although myoclonus is obviously the most common sign, other presentations, including tremor, chorea and dystonia are possible, thus proving that a movement disorder can be caused by a seizure. Other areas of values need to be acknowledged when publishing on the usual manifestation of usual conditions. An obvious one is very large descriptive series that enable precise estimation of statistics for various features. An example is the large multi-center descriptive series of patients with blepharospasm conducted by the Dystonia Coalition, which has allowed a more accurate estimation of associated features, such as family history, sensory phenomena, psychiatric comorbidities, treatment response, etc.32 Series from under-represented parts of the world are also very useful, for example to see how they compare to more commonly reported series from Western countries. This is the case for large genetic studies (eg, genome-wide association studies) where the different genetic backgrounds certainly play a role,33 or comparison between healthcare systems and the resulting management differences, which might also explain differences in outcomes and prognoses.34, 35 Teaching how to approach the description of clinical features (semiology or phenomenology) for publishing is not easy and in this article we provided the reader with a number of examples. Ultimately it is a matter of astute observation, passion, curiosity, scientific rigor and—last but not least—experience. Table 2 summarizes the overarching ideas behind our examples, which emphasize that semiology or phenomenology (the science of studying signs) is not old-fashioned and has still a lot to offer even in current times where tools like genetics and neuroimaging seem to be taking center stage. New clinical signs, such as the "shoulder tap test" for functional movement disorders,36 are routinely published. These new signs are not mere curiosities, but contribute to the easier identification of these disorders. Some might, reason why a reappraisal and comparison of their accuracy is worthwhile from time to time. For example, the "floating door sign" while drawing a house37 and denser Archimede's spirals38 have both linked to Parkinsonian tremor, although a subsequent comparative study has only shown that the latter can be useful.39 Some of these signs can be described in a creative and easy-to-remember way: "Superficial brain stimulation" to overcome freezing of gait or "Flamenco dance posture" to describe Parkinson's disease patients able to walk when touching their temples or presenting with characteristic arm dystonia are just some examples.40, 41 Of note, even established signs can be re-evaluated in a different context and provide useful information. Tremor is a very common movement disorder, although it remains a source of confusion and debate among experts. Thus, it still offers many opportunities for research. What is the role of "soft signs" in ET plus?42 Can ET present with isolated tremor of the head or voice, without obvious co-existing tremor of the hands?43, 44 What is the clinical meaning of lower limb involvement in ET?45 These are just some examples of research questions, which led to the understanding that lower limb involvement is more common in Parkinson's disease or functional tremor or that the inter-rater consistency of soft signs detection is rather disappointing even among experts. Finally, the beauty of reporting interesting clinical signs relies on its simplicity: careful description, nicely shot videos (even better if prospectively collected) and clever use of simple tools make the difference. Often a stopwatch or counting the blink rate is all you need, as shown in a study demonstrating that more than 27 blinks/minute at rest has a sensitivity and specificity of 90.0% and 70.9% for the diagnosis of blepharospasm.46 In conclusion, we hope that this article will stimulate more interest in careful reporting of clinical semiology or phenomenology. There is still a lot to learn. All authors had full access to all the data and accept responsibility to submit for publication. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. A.F.: 1A, B, C; 3A, B. H.A.J.: 1A, B, C; 3A, B. Ethical Compliance Statement: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. We also confirm that the approval of an institutional review board/ patient consent was not required for this work. Funding Sources and Conflict of Interest: This work was supported in part by NIH grant NS124764 along with grants to the Dystonia Coalition (U54 NS065701, U54 TR001456, and U54 NS116025), a consortium of the Rare Diseases Clinical Research Network (RDCRN) that is supported by the Office of Rare Diseases Research (ORDR) at the National Center for Advancing Clinical and Translational Studies (NCATS) in collaboration with the National Institute of Neurological Diseases and Stroke (NINDS) (HAJ) and by the Chair in Neuromodulation of the University Health Network and University of Toronto (AF). Financial Disclosure for the Previous 12 Months: HAJ has active or recent grant support from the US government (National Institutes of Health), private philanthropic organizations (Cure Dystonia Now), and industry (Revance Therapeutics, Inc.). HAJ has also served on advisory boards or as a consultant for Abbvie, Addex, Atlas, CoA Therapeutics, Cavion, EnePharmaceuticals, Ipsen, Merz, Neurocrine, Retrophin, Revance, and Takaha. He has received honoraria or stipends for lectures or administrative work from the International Parkinson's Disease and Movement Disorders Society. HAJ serves on the Scientific Advisory Boards for several private foundations including the Benign Essential Blepharospasm Research Foundation and the Dystonia Medical Research Foundation. He is also principal investigator for the Dystonia Coalition, which has received the majority of its support through the NIH (grants NS116025, NS065701 from the National Institutes of Neurological Disorders and Stroke TR001456 from the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences). The Dystonia Coalition has received additional material or administrative support from industry sponsors (Allergan Inc. and Merz Pharmaceuticals) as well as private foundations (The Benign Essential Blepharospasm Foundation, Cure Dystonia Now, The Dystonia Medical Research Foundation, and The National Spasmodic Dysphonia Association). AF has stock ownership in Inbrain Pharma and has received payments as consultant and/or speaker from Abbvie, Abbott, Boston Scientific, Ceregate, Dompé Farmaceutici, Inbrain Neuroelectronics, Ipsen, Medtronic, Iota, Syneos Health, Merz, Sunovion, Paladin Labs, UCB, Sunovion. He has received research support from Abbvie, Boston Scientific, Medtronic, Praxis, ES and receives royalties from Springer.