Clinical overview and phenomenology of movement disorders

Categories of movements

Movements can be categorized into one of four classes: automatic, voluntary, semivoluntary (also called unvoluntary) ( ; ; ), and involuntary ( )]. Automatic movements are learned motor behaviors that are performed without conscious effort, for example, walking an accustomed route and tapping of the fingers when thinking about something else. Voluntary movements are intentional (planned or self-initiated) or externally triggered (in response to some external stimulus, such as turning the head toward a loud noise or withdrawing a hand from a hot plate). Intentional voluntary movements are preceded by the Bereitschaftspotential (or readiness potential), a slow negative potential recorded over the supplementary motor area and contralateral premotor and motor cortex appearing 1 to 1.5 seconds before the movement. The Bereitschaftspotential does not appear with other movements, including the externally triggered voluntary movements ( ). In some cases, learned voluntary motor skills are incorporated within the repertoire of the movement disorder, such as camouflaging choreic movements or tics by immediately following them with voluntarily executed movements, so-called parakinesias. Semivoluntary (or unvoluntary ) movements are induced by an inner sensory stimulus (e.g., need to “stretch” a body part or need to scratch an itch) or by an unwanted feeling or compulsion (e.g., compulsive touching or smelling). Many of the movements occurring as tics or as a response to various sensations (e.g., akathisia and restless legs syndrome) can be considered unvoluntary because the movements are usually the result of an action to nullify an unwanted, unpleasant sensation. Unvoluntary movements usually are suppressible. Involuntary movements are often nonsuppressible (e.g., most tremors and myoclonus), but some can be partially suppressible (e.g., some tremors, chorea, dystonia, stereotypies, and some tics) ( ).

The origins of abnormal movements

Many movement disorders are associated with pathologic alterations in the basal ganglia or their connections. The basal ganglia are that group of gray matter nuclei lying deep within the cerebral hemispheres, that is, telencephalon (caudate, putamen, and pallidum), the diencephalon (subthalamic nucleus), the mesencephalon (substantia nigra), and the mesencephalic-pontine junction (pedunculopontine nucleus) (see Chapter 3 ). There are some exceptions to this general rule. Pathologic conditions of the cerebellum or its pathways typically result in impairment of coordination (asynergia, ataxia), misjudgement of distance (dysmetria), and intention tremor. Myoclonus and many forms of tremors do not appear to be related primarily to basal ganglia pathologic conditions, and often arise elsewhere in the central nervous system, including cerebral cortex (cortical reflex myoclonus), brainstem (cerebellar outflow tremor, reticular reflex myoclonus, hyperekplexia, and rhythmical brainstem myoclonus such as palatal myoclonus/tremor and ocular myoclonus), and spinal cord (rhythmic segmental myoclonus and nonrhythmic propriospinal myoclonus). Moreover, many myoclonic disorders are associated with diseases in which the cerebellum is involved, such as those causing the Ramsay Hunt syndrome of progressive myoclonic ataxia (see Chapter 18 ). The peripheral nervous system also can give rise to abnormal movements, such as the painful legs–moving toes syndrome ( ). It is not known for certain which part of the brain is associated with tics, although the basal ganglia and the limbic structures have been implicated. Certain localizations within the basal ganglia are classically associated with specific movement disorders: substantia nigra with bradykinesia and rest tremor, subthalamic nucleus with ballism, caudate nucleus with chorea, and putamen with dystonia.

Movement disorders can be isolated (i.e., present and manifest only as a movement disorder) or can be combined with other neurologic abnormalities. They can be caused by endocrine disorders and disease of internal organs (see review by ), and, as uncovered in the last dozen years, and discussed later, they can be due to genetic mutations and immunologic dysfunction

Historical perspective

The neurologic literature contains a number of seminal papers, reviews, and books that emphasized and established movement disorders as associated with basal ganglia pathologic conditions ( ; ; ; ; ; ; ; ; ). Before the term movement disorders was created, most of the conditions now included under that heading were commonly called extrapyramidal disorders, a label coined by to associate these conditions with the basal ganglia. In his review on the classification of movement disorders, explains both the origin of the term movement disorders and the reasons why extrapyramidal is not an accurate label.

A historical perspective of movement disorders can be gained by listing the dates when the various clinical entities were first introduced ( Table 1.2 ).

Epidemiology

Movement disorders are common neurologic problems, and epidemiologic studies are available for some of them ( Table 1.3 ). There have been several studies for Parkinson disease (PD), and these have been carried out in several countries ( ; ). Table 1.3 lists the prevalence rates of some movement disorders. The frequency of different types of movement disorders seen in the two specialty clinics at Columbia University and Baylor College of Medicine is presented in Table 1.4 . More detailed information is provided in the relevant chapters for specific diseases.

Genetics

A large number of movement disorders are genetic in etiology; many of the diseases have now been mapped to specific regions of the genome, and a good proportion of them have been localized to a specific gene ( Table 1.5 ). The number of new genes or gene loci found is growing at a rapid rate. For example, in the previous edition of this book, 16 genetic loci had been identified with the PD label, coded as PARK. That number reached 23 at the time of finalizing this edition. Many other genetic mutations result in parkinsonism without the designation PARK (see Chapter 5 ). A comprehensive list of movement disorders whose genes have been mapped or identified are listed in Table 1.5 . Three detailed chapters ( ; ) have been published specifically related to movement disorder genetics. The MDS Task Force on nomenclature of genetic movement disorders made a recommendation ( ) for a new naming scheme that markedly differs from the one proposed by molecular geneticists and used for several decades. This geneticist-created nomenclature system uses symbols to represent disease phenomenology (e.g., PARK for parkinsonism, DYT for dystonia) followed by sequential numerals that were assigned chronologically as new gene loci and gene identifications were made. The MDS Task Force pointed out problems with this scheme; a major one for the field of movement disorders is the inclusion of paroxysmal movement disorders into the DYT label.

The Task Force made a major contribution with its new nomenclature. It is more rigorous by including only identified genes, not conditions with just chromosomal mapping. A major change was the naming of a gene by its major phenotype (e.g., PARK, DYT, CHOR, PxMD) followed by a gene name, not a numeral. A major problem, though, is that it is almost impossible for clinicians to recall the exact names of genes, and chromosomal loci without an identified gene are excluded in the Task Force classification. The old, original numeral nomenclature is much easier to recall and to pronounce. If a gene mutation causes more than one phenotype, both labels are used in the Task Force system, assigning more than one name to a gene (e.g., PARK/DYT). The Task Force also allows labels for distinctive imaging features (e.g., brain iron accumulations and brain calcifications). The Task Force system eliminates risk factor genes and allows only disease-causing genes. Finally, the Task Force requires confirmatory studies before a new gene locus can be labeled in the scheme. Table 1.5 uses the older nomenclature, which includes both disease-causing and risk factor genes. There is a major advantage to being all inclusive for the clinician. In addition, Table 1.5 includes genes with mapped loci, but not yet identified genes, because this inclusion also aids the clinician to identify specific etiologies.

points out that the Task Force nomenclature emphasizes the predominant phenotype of a given genotype, but the phenotypes can vary with the same genotype. A mutant gene with many phenotypes is more difficult and cumbersome to label in this new nomenclature.

Several inherited movement disorders are due to expanded repeats of the trinucleotide cytosine-adenine-guanine (CAG), and other expanded trinucleotide repeats (e.g., Friedreich ataxia is due to repeats of guanine-adenine-adenine (GAA). Normal individuals contain an acceptable number of these trinucleotide repeats in their genes, but these triplicate repeats are unstable and when expanded lead to disease ( Table 1.6 ). Neurogenetics is one of the fastest moving research areas in neurology, so the list in Table 1.5 keeps expanding rapidly.

Many of the inherited diseases listed in Table 1.5 are rare. An MDS task force reported that more than 30 rare inherited movement disorders are treatable ( ). Some of these are designated as inborn errors of metabolism. This term has been applied to inherited diseases with an alteration in some enzymatic metabolic process. Often such genetic defects result in an accumulation of a metabolic substrate that failed to be degraded. In other entities the failure to produce an essential compound leads to a functional deficit. Hundreds of rare inborn errors of metabolism have been described, especially with the development of next-generation sequencing. Most of these disorders begin in childhood, but adult onset is not uncommon. Ebrahimi-Fakhari and colleagues (2019) reviewed the inborn errors of metabolism that can manifest with a movement disorder. This review is particularly valuable because it caters to the clinician by classifying these disorders by the movement phenomenology. Furthermore, the authors present 10 of the treatable ones so that the clinician will be able to single these out and hopefully not miss them. These 10 conditions in rank order are Wilson disease, hypermanganesemia, dopa-responsive dystonia, Niemann-Pick type C, glutaric aciduria type 1, glut1 deficiency syndrome, cerebrotendinous xanthomatosis, cerebral folate deficiency, biotin- and thiamine-responsive basal ganglia disease, and ataxia with vitamin E deficiency. Each of these disorders can manifest with different phenomenologies, the most common being dystonia and ataxia. Other abnormal movements, such as parkinsonism, tremor, and myoclonus, are often incorporated into the clinical presentation.

Autoimmune disorders as a cause of movement disorders

Symptoms and signs of disease in medicine can have a wide range of etiologies, including genetic, infectious, traumatic, vascular, and psychogenic, among others. In the chapters in this book covering the various phenomenologies and syndromes, possible etiologies of each phenomenology are listed. Autoimmune etiologies have become more recognized in recent years as inducing a wide variety of neurologic disorders, including movement disorders. Some, such as lupus erythematosus and antiphospholipid antibody syndrome, may induce their neurologic symptoms secondarily through vascular involvement. Others directly affect the neurons or glia to induce symptoms. Stiff-person syndrome is one of the early recognized autoimmune movement disorders (see Chapter 21 ). The first antibody recognized in stiff-person syndrome was against the enzyme glutamic acid decarboxylase. Since then, antibodies against amphiphysin, dipeptidyl-peptidase–like protein-6 (DPPX), gamma-aminobutyric acid type A receptor (GABAAR), glycine receptor (GlyR), and glycine transporter 2 (GlyT2) have been reported ( ). Thus, despite different etiologic triggers, the resulting motor phenomenology is the same.

Antibodies derived in response to a variety of tumors can result in the autoimmune disorders known as paraneoplastic syndromes. There have been numerous case reports of a variety of movement disorders being caused by a variety of cancers. Published reviews of these paraneoplastic movement disorders have helped organize our understanding of them ( ; ; ; ; ). Most affected individuals are adults over the age of 50 years. One of the most striking dyskinesias predominantly affecting the oral area (but also limbs) with stereotypic, nonceasing movements is the encephalitis caused by the antibody to the N-methyl-D-aspartate receptor (anti-NMDAR), initially reported by Dalmau and colleagues (2007). All ages have been affected, and although ovarian cancer is the most common source, boys with teratomas also have been reported. Video 1.1 is an example of the characteristic anti-NMDAR–induced encephalitis with stereotypies, particularly affecting the oral region.

Video 1.1 Anti-NMDA Receptor encephalitis.

As a group, paraneoplastic movement disorders have a subacute onset with rapid evolution. There is often a mixture of more than one phenotype. One type of cancer can cause different neurologic phenotypes, and one phenotype can be caused by different types of cancers. Many paraneoplastic movement disorders can be treated by removing the tumor and instigating pharmacotherapy against the autoimmunity. Therefore, early diagnosis by recognizing the different phenotypes is important. A fairly common paraneoplastic movement disorder is opsoclonus-myoclonus.

Many other autoimmune causes of movement disorders besides neoplasms have been identified. These are the ones that can cause the chorea in Sydenham disease, the ataxia of celiac disease, and the parkinsonism/dystonia in Sjögren syndrome. reviewed these and paraneoplastic causes of movement disorders. Celiac disease as a cause of ataxia is discussed in Chapter 20 . Cortical myoclonus associated with celiac disease is less common ( ; ; ). Despite the cerebral cortex being electrophysiologically associated with the myoclonus, autopsies have reported pathologic findings only in the cerebellum in these cases. One feature emphasized by Bhatia and colleagues (1995) is a characteristic myoclonus affecting just the legs in celiac disease. An example of such a case in which there are correlates of electrical discharges in the electroencephalogram (EEG) involving the leg area of the cerebral cortex is presented in Video 1.2 in the discussion of myoclonus. Faciobrachial dystonic seizures are due to an autoimmune encephalitis caused by the Lgi1 antibody against the voltage-gated potassium channel ( ) ( Video 1.3 ) and is discussed within the dystonia section in this chapter. Technically, faciobrachial dystonic seizures are categorized as a seizure disorder and not a true movement disorder, but they mimic dystonic movements in some fashion and hence the name of the phenomenology is appropriate. A thorough review covering immune disorders resulting in abnormal movement was published by ]. Some patients with multiple system atrophy (MSA) have been found to have neuropathology changes consisten with Sjögren disease, an autoimmune disorder ( ).

Video 1.2 Leg myoclonus.

Video 1.3 Faciobrachial dystonic seizures.

Quantitative assessments

The assessment of severity of disease is a process that is carried out by all clinicians when evaluating a patient. Quantifying the severity provides the means to monitor the progression of the disorder and the effect of intervention by pharmacologic or surgical approaches. Many mechanical and electronic devices, including accelerometers, can quantitate specific signs, such as tremor, rigidity, and bradykinesia. These have been developed by physicians and engineers over at least 90 years ( ; ), and newer computerized devices continue to be conceived and developed ( ; ; ; ; ; ). New wrist-wearing devices are being tested, and applications have been developed for smartphones to help electronically quantify abnormal movements and severity of PD ( ; ), and in time these may become useful tools.

The advantages of mechanical and electronic measurements are objectivity, consistency, uniformity among different investigators, and rapidity of database storage and analysis. However, these measurements might not be as sensitive than more subjective clinical measurements. In one study comparing objective measurements of reaction and movement times with clinical evaluations, found the latter to be more sensitive. Small wearable devices and smartphone applications are being developed to quantify movement patterns ( ; ; ; ; ), and these may become useful tools someday.

The mechanical and electronic methods of measurement have other disadvantages. Instrumentation can usually measure only a single part of the body, measure only a single sign, and measure at a single point in time. Data-stored computerized devices, however, have an advantage of obtaining measurements over a long period. Disorders such as parkinsonism encompass a wide range of motor abnormalities and behavioral features. Clinical measurements can cover a wider range of the parkinsonian spectrum of impairments and have the advantage of being performed at the bedside or in the office or clinic at the time the patient is being examined by the physician. Equally important, clinical assessment can evaluate disability in terms of activities of daily living (ADLs), and the one developed by and modified slightly ( ) has proven highly useful.

A number of clinical rating scales have been proposed (e.g., see ). Several that are now considered standards and are in wide use can be recommended: the Unified Parkinson’s Disease Rating Scale (UPDRS) ( ) is the standard scale for rating severity of signs and symptoms of PD; a videotaped demonstration of the assigned ratings has been published ( ). A modification of the UPDRS by the MDS has been completed ( ) and is known as the MDS-UPDRS. It has several advantages, namely assessing milder signs, better written definitions, and expanding the assessment of tremor and nonmotor symptoms in PD. A videotaped demonstration of the assigned ratings for the component of MDS-UPDRS also has been published ( ). A mathematical correlation of scores between the UPDRS and MDS-UPDRS has been calibrated ( ). The nonmotor component of the MDS-UPDRS has been found to correlate well with a specific Non-Motor Symptoms Scale for Parkinson Disease ( ). Other standard scales for PD and its complications are the Schwab and England Activities of Daily Living Scale for parkinsonism ( ) as modified ( ); the Hoehn and Yahr Parkinson Disease Staging Scale ( ) as modified ( ); the Unified Dyskinesia Rating Scale ( ), which, compared with other dyskinesia rating scales, was found to be superior in detecting change in a controlled clinical trial testing a drug for dopa-induced dyskinesias ( ); the Parkinson Psychosis Rating Scale ( ); the daily diary to record fluctuations and dyskinesias ( ); the Core Assessment Program for Intracerebral Transplantation ( ); the Progressive Supranuclear Palsy Rating Scale ( ), the Fahn-Marsden Dystonia Rating Scale ( ); the Unified Dystonia Rating Scale ( ); the Toronto Western Spasmodic Torticollis Rating Scale (TWSTERS) for cervical dystonia ( ); the Fahn-Tolosa-Marin clinical rating scale for tremor ( ); the Bain tremor scale ( ); the Essential Tremor Rating Assessment Scale (TETRAS) ( ); and the Unified Huntington’s Disease Rating Scale, which also has a published videotaped demonstration of assigned ratings ( ).

Akinesia/bradykinesia

Akinesia, bradykinesia, and hypokinesia literally mean “absence,” “slowness,” and “decreased amplitude” of movement, respectively. The three terms are commonly grouped together for convenience and usually referred to under the term bradykinesia. These phenomena are a prominent and most important feature of parkinsonism and are often considered a sine qua non for parkinsonism. In fact, the presence of bradykinesia is a necessary sign for the diagnosis of PD according to the UK Parkinson Disease Society’s Brain Bank criteria ( ). Although akinesia means “lack of movement,” the label is often used to indicate a very severe form of bradykinesia ( Video 1.4 ). Bradykinesia is mild in early PD and becomes more severe as the disease worsens; a similar pattern is seen in other forms of parkinsonism. A discussion of the phenomenology of akinesia/bradykinesia requires a brief description of the clinical features of parkinsonism, presented here. A fuller discussion is presented in Chapter 4 .

Video 1.4 Akinesia/bradykinesia/hypokinesia.

Parkinsonism is a neurologic syndrome manifested by any combination of six independent, nonoverlapping cardinal motor features: tremor-at-rest, bradykinesia, rigidity, flexed posture, freezing, and loss of postural reflexes ( Table 1.7 ). At least two of these six cardinal features should be present before the diagnosis of parkinsonism is made, one of them being bradykinesia, as mentioned previously. There are many causes of parkinsonism; they can be divided into five major categories: primary, secondary, parkinsonism-plus disorders, heredodegenerative disorders, and benign parkinsonism ( Table 1.8 ). Primary parkinsonism (PD) is a progressive disorder of unknown etiology or of a known gene mutation, and the diagnosis is usually made by excluding other known causes of parkinsonism ( ). The complete classification of parkinsonian disorders is presented in Chapter 4 . The specific diagnosis of the type of parkinsonism depends on details of the clinical history, the neurologic examination, and laboratory tests.

The primary parkinsonism disorder known as Parkinson disease (PD), often referred to as idiopathic parkinsonism, is the most common type of parkinsonism encountered by the neurologist. But drug-induced parkinsonism (a secondary parkinsonism) is probably the most common form of parkinsonism ( Video 1.5 ) because neuroleptic drugs (dopamine receptor– blocking agents), which cause drug-induced parkinsonism, are widely prescribed for treating psychosis (see Chapter 17 ). Here, some of the motor phenomenology of parkinsonism is discussed as part of the overview of the differential diagnosis of movement disorders based on phenomenology.

Video 1.5 Drug-induced parkinsonism.

PD begins insidiously. Tremor is usually the first symptom recognized by the patient. However, the disorder can begin with slowness of movement, shuffling gait, painful stiffness of a shoulder, micrographia, or even depression or rapid eye movement (REM) sleep behavior disorder. In the early stages, the motoric symptoms and signs tend to remain on one side of the body ( Video 1.6 ), but with time the other side slowly becomes involved as well.

Video 1.6 Unilateral PD.

Tremor is present in the distal parts of the extremities and the lips while the involved body part is “at rest.” “Pill-rolling” tremor of the fingers and flexion–extension or pronation–supination tremor of the hands are the most typical (see Video 1.6 ). The tremor ceases on active movement of the limb but can reemerge when the limb remains in a posture against gravity. Resting tremor must be differentiated from postural and kinetic tremors, in which tremor appears only when the arm is being used. These tremors are typically caused by other disorders, namely essential tremor and cerebellar disorders. An occasional patient with PD will have an action tremor of the hand instead of or in addition to tremor-at-rest ( Video 1.7 ). In the cranial structures, the lips, chin, and tongue are the predominant sites for tremor ( Video 1.8 , whereas head (neck) tremor, although it can occur in PD, is more typical of essential tremor, cerebellar tremor, and dystonic tremor.

Video 1.7 Postural and action tremor in a patient with PD.

Video 1.8 Jaw tremor as well as hand tremor in a patient with PD.

Akinesia/bradykinesia/hypokinesia manifests cranially by masked facies (hypomimia), decreased frequency of blinking, impaired upgaze, impaired ocular convergence, soft speech (hypophonia), loss of inflection (aprosody), and drooling of saliva because of decreased spontaneous swallowing ( Video 1.9 ). When examining cranial structures, one should look for other signs of PD or Parkinson-plus syndromes. Repetitive tapping the glabella often reveals nonsuppression of blinking (Myerson sign) in patients with PD ( ) ( Video 1.10 ), whereas blinking is normally suppressed after two or three blinks ( ). Eyelid opening after the eyelids were forcefully closed is usually normal in PD but may be markedly impaired in progressive supranuclear palsy (PSP); this has been called “apraxia of eyelid opening” ( Video 1.11 ) even though the term apraxia is a misnomer. The eyes looking straight ahead are typically quiet in PD, but in some Parkinson-plus syndromes, square wave jerks may be seen, especially in PSP ( Video 1.12 ). Ocular movements are usually normal in PD, except for impaired upgaze and convergence. When saccadic eye movements are impaired, and especially when downgaze is impaired, a Parkinson-plus syndrome such as PSP or corticobasal degeneration (CBD) is usually indicated ( ) ( Video 1.13 ).

Video 1.9 Masked face and drooling of saliva.

Video 1.10-6 Myerson sign.

Video 1.11 Apraxia of eyelid opening.

Video 1.12 Square wave jerks.

Video 1.13 Impaired ocular movements.

In the arms, bradykinesia is manifested by slowness in shrugging or relaxing the shoulder ( Video 1.14 ); slowness in raising the arm; loss of spontaneous movement such as gesturing; smallness and slowness of handwriting (micrographia); slowness and decrementing amplitude of repetitively opening and closing the hands, tapping a finger, and twisting the hand back and forth; difficulty with hand dexterity for shaving, brushing teeth, and putting on makeup; and decreased arm swing when walking. In the legs, bradykinesia is manifested by slowness and decrementing amplitude in repetitively stomping the foot or tapping the toes; by slowness in making the number 8 with the foot; and by a slow, short-stride, shuffling gait with reduced heel strike when stepping forward. Typically in PD, there is a narrow base, that is, the feet are close together when the patient walks. In the trunk, bradykinesia is manifested by difficulty arising from a chair, getting out of automobiles, and turning in bed.

Video 1.14 Decreased shouldershrug, decrementing rapid successive movements, and decreased armswing due to bradykinesia.

Bradykinesia encompasses a loss of automatic movements and slowness in initiating movement on command and reduction in amplitude of the voluntary movement. An early feature of reduction of amplitude is the decrementing of the amplitude with repetitive finger tapping or foot tapping (see Video 1.14 ), which also manifests by impaired rhythm of the tapping. Decreased rapid successive movements both in amplitude and speed are characteristic of bradykinesia regardless of the etiology of parkinsonism ( Video 1.15 ). Carrying out two activities simultaneously is impaired ( ), and this difficulty may be a manifestation of bradykinesia ( ). With the stimulation of a sufficient sensory input, bradykinesia, hypokinesia, and akinesia can be temporarily overcome (kinesia paradoxica) ( Video 1.16 ).

Video 1.15 1 Decreased rapid successive movements in juvenile Huntington disease.

Video 1.16 Overcoming akinesia.

Rigidity (described later) is another cardinal feature of parkinsonism. Rigidity usually manifests in the distal limbs by a ratchety “give” when a joint is passively moved throughout its range of motion, so-called cogwheel rigidity. Rigidity of proximal joints is easily appreciated by the examiner swinging the shoulders (Wartenberg sign) ( Video 1.17 ), flexing and extending the elbows, or rotating the hips. The patient often complains of stiffness of the neck, which is due to rigidity; the neck is a common location for rigidity. In patients with atremulous PD and in whom the disease remains manifest unilaterally for several years, a pseudohemiplegic gait pattern can be seen because of the combination of rigidity and akinesia. The patient has dragging of the affected leg and does not swing the affected arm, which is flexed at the elbow ( Video 1.18 ).

Video 1.17 Shoulder rigidity manifested by decreased armswing with passive movement of the shoulders.

Video 1.18 Pseudohemiplegic gait in young-onset PD.

As the disease advances, the patient begins to assume a flexed posture, particularly of the neck, thorax, elbows, hips, and knees. The patient begins to walk with decreased arm swing and then with the arms flexed at the elbows and the forearms placed in front of the body. With the knees slightly flexed, the patient tends to shuffle the feet, which stay close to the ground and are not lifted up as high as they would be in normal persons; with time there is loss of heel strike, which would normally occur when the foot moving forward is placed on the ground. Eventually, the flexion can become extreme ( Video 1.19 ), leading to camptocormia ( ) or pronounced kyphoscoliosis with truncal tilting.

Video 1.19 Flexed posture.

Loss of postural reflexes occurs later in the disease. The patient has difficulty righting himself or herself after being pulled or tilted off balance ( ). A simple test (the “pull test”) for the righting reflex is for the examiner to stand behind the patient and give a firm tug on the patient’s shoulders toward the examiner, explaining the procedure in advance and directing that the patient should try to maintain balance by taking a step backward ( ; ). Typically, after a practice pull, a normal person can recover within two steps ( Video 1.20 ). A mild loss of postural reflexes can be detected if the patient requires several steps to recover balance. A moderate loss is manifested by a greater degree of retropulsion. With a more severe loss the patient would fall if not caught by the examiner ( Video 1.21 ), who must always be prepared for such a possibility. With a marked loss of postural reflexes, a patient cannot withstand even a gentle tug on the shoulders or cannot stand unassisted without falling. To avoid having the patient fall to the ground, the examiner must always be prepared to catch the patient ( Video 1.22 ). It is wise to have a wall behind the examiner when the pull test is being performed. This is essential if the patient is a large or bulky individual ( Video 1.23 ); with this insurance against falling, one can perform a pull test on any individual.

Video 1.20 Normal pull test.

Video 1.21 Examples of abnormal (positive) pull tests.

Video 1.22 Always be prepared to catch a patient when performing the Pull Test:

Video 1.23 Performing the Pull Test on very large patients:

A combination of loss of postural reflexes and stooped posture can lead to festination, in which the patient walks faster and faster, eventually running, trying to catch up with his or her center of gravity to prevent falling ( Video 1.24 ).

Video 1.24 Festinating gait.

Akinesia needs to be distinguished from the freezing phenomenon, both of which are features of parkinsonism. The freezing phenomenon ( ) affects gait more than other parts of the body and begins either with start-hesitation—that is, the feet take short, sticking, shuffling steps when the patient initiates walking—or when turning while walking ( Videos 1.25 and 1.26 ). With progression, the feet become “glued to the ground” when the patient walks through a crowded space (e.g., a row of seats in a theater or a revolving door) or is trying to move in the presence of a time restriction (e.g., crossing the street at the green light or entering an elevator before the door closes). Often, patients develop destination-freezing—that is, stopping before reaching the final destination. For example, the patient might stop too soon when reaching a chair in which he or she intends to sit down ( Video 1.27 ). With further progression, sudden transient freezing can occur when the patient is walking in an open space or when the patient perceives an obstacle in the walking path. The freezing phenomenon can also affect arms and speech and is discussed in more detail under “Freezing” later in this chapter

Video 1.25 Freezing when turning and when starting to walk.

Video 1.26 Freezing while turning.

Video 1.27 Destination-freezing.

Sometimes severe orthostatic hypotension can mimic freezing of gait because the patient feels faint, the legs become wobbly and shaky, and the patient is unable to move because of the feeling of not being able to maintain an erect posture ( Video 1.28 ). Fear of falling is a type of gait disorder that needs to be differentiated from slowness of walking because of PD. Most people have fear of falling because they have fallen in the past and have subsequently become exceedingly cautious ( Video 1.29 ). Fear of falling can develop in people who have not fallen ( Video 1.30 ). Extreme cases of fear of falling can be due to agoraphobia, which is fear of being in an open space, a psychiatric anxiety disorder ( Video 1.31 ).

Video 1.28 Shaky legs when standing with onset of orthostatic hypotension.

Video 1.29 Fear of falling.

Video 1.30 Fear of Falling in a person who had not fallen.

Video 1.31 Gait disorder due to agoraphobia.

In addition to these motor signs, most patients with PD have behavioral signs. Bradyphrenia is mental slowness, analogous to the motor slowness of bradykinesia. Bradyphrenia is manifested by slowness in thinking or in responding to questions. It occurs even when PD begins at a young age and is more common than dementia. The “tip-of-the-tongue” phenomenon ( ), in which a patient cannot immediately come up with the correct answer but knows what it is, may be a feature of bradyphrenia. With time, the parkinsonian patient gradually becomes more passive, indecisive, dependent, and fearful. The spouse gradually makes more of the decisions and becomes the dominant voice. Eventually, the patient would sit much of the day unless encouraged to do activities. Passivity and lack of motivation also are expressed by the patient not desiring to attend social events. The term abulia is used to describe such severe apathy, loss of mental and motor drive, and blunting of emotional, social, and motor expression. Abulia encompasses loss of spontaneous and responsive motor activity and loss of spontaneous affective expression, thought, and initiative.

Depression is a frequent feature in patients with PD, being obvious in around 30% of cases. The prevalence of dementia in PD is about 40%, but the proportion increases with age. Below the age of 60 years, the proportion with dementia is about 8%; older than 80 years, it is 69% ( ). Following PD patients over time, about 80% develop dementia ( ; ). The risk for death is markedly increased when a PD patient becomes demented ( ).

The age at onset of PD is usually above the age of 40, but younger patients can be affected. Onset between ages 20 and 40 is called young-onset Parkinson disease (YOPD); but the trend today is to label onset below age 50 as YOPD. People with YOPD usually develop pronounced levodopa-induced dyskinesias and motor fluctuations ( Videos 1.32A , B ). Onset before age 20 is called juvenile parkinsonism. Juvenile parkinsonism does not preclude a diagnosis of PD ( Video 1.33 ), but it raises questions of other etiologies, even with dopa-responsive parkinsonism, such as neurodegenerations with brain iron accumulation ( Video 1.34 ), and other degenerations. Non–dopa-responsive cases of juvenile parkinsonism include (see Video 1.9 ), the Westphal variant of Huntington disease (HD) (see Video 1.15 ), and neuroleptic-induced parkinsonism ( Video 1.36 ). In addition, familial and sporadic primary juvenile PD often do not show the typical pathologic hallmark of Lewy bodies ( ). A number of autosomal recessive genes such as PRKN, PINK1, and DJ1 (see Chapter 5 ) can cause juvenile PD without the presence of Lewy bodies. One needs to be aware when reading the literature that in Japan onset before age 40 is called juvenile parkinsonism. Juvenile parkinsonism with spasticity can occur in the hereditary spastic paraplegias known as SPG11 ( ; ; ) and SPG15 ( ; ).

Video 1.32A Young-onset Parkinson disease (YOPD) with levodopa-induced peak-dose dystonia:

Video 1.32B Young-onset Parkinson disease (YOPD) with Super OFFs at the beginning and end of a levodopa response

Video 1.33 Juvenile Parkinson disease.

Video 1.34 Juvenile onset akinetic-rigid-dystonic syndrome in a child with neuronal degeneration with brain iron accumulation (NBIA).

Video 1.35 Juvenile onset tremulous parkinsonism that progressed to become akinetic, rigid, dystonic syndrome with speech involvement and eventually dementia and bed-ridden.

Video 1.36 Oculogyric crisis and parkinsonism due to neuroleptic treatment.

PD is more common in men, with a male-to-female ratio of 3:2. The incidence in the United States is 20 new cases per 100,000 population per year ( ), with a prevalence of 187 cases per 100,000 population ( ). For the population over 40 years of age, the prevalence rate is 347 per 100,000 ( ). With the introduction of levodopa the mortality rate dropped from 3-fold to 1.5-fold above normal. But after the first wave of impaired patients becoming improved with this new and effective treatment, the mortality rate for PD gradually climbed back to the pre-levodopa rate ( ).

Apraxia

Apraxia is a cerebral cortex, not a basal ganglia, dysfunction. Apraxia is traditionally defined as a disorder of voluntary movement that cannot be explained by weakness, spasticity, rigidity, akinesia, sensory loss, or cognitive impairment. It can exist and be tested for in the presence of a movement disorder provided that akinesia, rigidity, or dystonia is not so severe that voluntary movement cannot be executed. The classic work of defined three categories of apraxia.

• 1.

  In ideational apraxia the concept or plan of movement cannot be formulated by the patient. Some examiners test for ideational apraxia by asking the patient to perform a series of sequential movements such as pretending to fill a pipe, lighting it, and then smoking, or putting a letter into an envelope, sealing it, and then affixing a stamp. Ideational apraxia is due to parietal lesions, most often diffuse and degenerative.

• 2.

  In ideomotor apraxia the concept or plan of movement is intact, but the individual motor engrams or programs are defective. Ideomotor apraxia is commonly tested for by asking patients to undertake specific motor acts to verbal or written commands, such as waving goodbye, saluting like a soldier, combing their hair, or using a hammer to fix a nail, etc. The patients with ideomotor apraxia often improve their performance if asked to mimic the action when the examiner shows them what to do or when given the object or tool to use. Ideomotor apraxia usually does not interfere with normal spontaneous motor actions but requires specific testing for its demonstration. It usually, but not always, is associated with aphasia and is due mainly to lesions in the dominant hemisphere, particularly in the parietotemporal regions, the arcuate fasciculus, or the frontal lobe; such ideomotor apraxia is bilateral, provided there is not a hemiplegia. Lesions of the corpus callosum can cause apraxia of the nondominant hand.

• 3.

  Limb-kinetic apraxia is the least understood type. It refers to a higher order motor deficit in executing motor acts that cannot be explained by simple motor impairments. It has been attributed to lesions of premotor regions in the frontal lobe, such as the supplementary motor area.

The concepts of apraxia are being refined into more discrete identifiable syndromes as knowledge of the functions of the cortical systems controlling voluntary movement advances (for reviews, see ; ). A quick, convenient method for testing for apraxia at the bedside is to ask the patients to copy a series of hand postures shown to them by the examiner.

Ideomotor and limb-kinetic apraxias are found in a number of movement disorders, for example, CBD ( Videos 1.37 , 1.38 ) and PSP (see Chapter 9 ). A number of other phenomena reflecting cerebral cortex dysfunction may be seen in such patients. Patients with CBD frequently have signs of cortical myoclonus ( Video 1.39 ) or cortical sensory deficit. The alien limb phenomenon, also seen in CBD, consists of involuntary, spontaneous movements of an arm or leg ( Video 1.40 ), which curiously and spontaneously moves to adopt odd postures quite beyond the control or understanding of the patient. Intermanual conflict is another such phenomenon; one hand irresistibly and uncontrollably begins to interfere with voluntary action of the other. The abnormally behaving limb may also show forced grasping of objects, such as blankets or clothing. Such patients often exhibit other frontal lobe signs, such as a grasp reflex or utilization behavior, in which they compulsively pick up objects presented to them and begin to use them. For example, if a pen is presented with no instructions, they pick it up and write. If a pair of glasses is proffered, they place the glasses on the nose; if further pairs of glasses are then shown, the patient may end up with three or more spectacles on the nose!

Video 1.37 Apraxia.

Video 1.38 Other examples of apraxia.

Video 1.39 Cortical myoclonus.

Video 1.40 Alien limb.

Patients presenting with features of CBD may actually have other pathologic conditions, such as PSP and Alzheimer disease, instead of CBD. For this reason, until an autopsy can confirm the pathologic findings of CBD, the clinical presentation is now called corticobasal syndrome (CBS).

Blocking (holding) tics

Blocking (or holding) is a motor phenomenon that is seen occasionally in patients with tics and is characterized as a brief interference of social discourse and contact. There is no loss of consciousness, and, although the patient does not speak during these episodes, he or she is fully aware of what has been spoken. These blocking tics appear in two situations: (1) as an accompanying feature of some prolonged tics, such as during a protracted dystonic tic ( Video 1.41 ) or during tic status and (2) as a specific tic phenomenon in the absence of an accompanying obvious motor or vocal tic. The latter occurrences have the abruptness and duration of a dystonic tic or a series of clonic tics, but they do not occur during an episode of an obvious motor tic.

Video 1.41 Blocking tics.

Although both types can be called blocking tics, the first type can be considered “intrusions” because the interruption of activity is due to a positive motor phenomenon (i.e., severe, somewhat prolonged motor tics) that interferes with other motor activities. An example would be a burst of tics that is severe enough to interrupt ongoing motor acts, including speech, as seen in Video 1.41 .

The second type (i.e., inhibition of ongoing motor activity without an obvious “active” tic) can be considered a negative motor phenomenon, that is, a “negative” tic. The negative type of blocking tics should be differentiated from absence seizures or other paroxysmal episodes of loss of awareness. There is never loss of awareness with blocking tics. Individuals with intrusions and negative blocking recognize that they have these interruptions of normal activity and are fully aware of the environment during them, even if they are unable to speak at that time.

Cataplexy and drop attacks

Drop attacks can be defined as sudden falls with or without loss of consciousness, as a result of either collapse of postural muscle tone or abnormal muscle contractions in the legs ( Video 1.42 ). About two-thirds of cases are of unknown etiology ( ). Symptomatic drop attacks have many neurologic and nonneurologic causes. Neurologic disorders include leg weakness; sudden falls in parkinsonian syndromes, including those caused by freezing and orthostatic hypotension ( Video 1.28 ); transient ischemic attacks; epilepsy; myoclonus; startle reactions (hyperekplexia); paroxysmal dyskinesias; structural central nervous system lesions; and hydrocephalus. In some of these, there is loss of muscle tone in the legs, in others there is excessive muscle stiffness with immobility, such as in hyperekplexia. Syncope and cardiovascular disease account for nonneurologic causes. Idiopathic drop attacks usually appear between the ages of 40 and 59 years, the prevalence increasing with advancing age ( ), and are a common cause of falls and fractures in the elderly ( ; ). A review of drop attacks has been provided by .

Video 1.42 Drop attack due to hyperekplexia (excessive startle):

Cataplexy is another cause of symptomatic drop attacks that does not fit the categories listed previously. Patients with cataplexy fall suddenly without loss of consciousness but with inability to speak during an attack. There is a precipitating trigger, usually laughter or a sudden emotional stimulus. The patient’s muscle tone is flaccid and remains this way for many seconds. Cataplexy is usually just one feature of the narcolepsy syndrome; other features include sleep paralysis and hypnagogic hallucinations, in addition to the characteristic feature of sudden, uncontrollable falling asleep. A review of cataplexy has been provided by .

Catatonia, psychomotor depression, and obsessional slowness

In 1874, Karl Ludwig Kahlbaum wrote the following description: “the patient remains entirely motionless, without speaking, and with a rigid, mask-like facies, the eyes focused at a distance; he seems devoid of any will to move or react to any stimuli; there may be fully developed ‘waxen’ flexibility, as in cataleptic states, or only indications, distinct, nevertheless, of this striking phenomenon. The general impression conveyed by such patients is one of profound mental anguish . . .” (from ).

defined catatonia as a syndrome characterized by catalepsy (abnormal maintenance of posture or physical attitudes), waxy flexibility (retention of the limbs for an indefinite period in the positions in which they are placed), negativism, mutism, and bizarre mannerisms. Patients with catatonia can remain in one position for hours and move exceedingly slowly to commands, usually requiring the examiner to push them along ( Videos 1.43 and 1.44A,B ). However, when moving spontaneously, they move quickly, such as when scratching themselves. In contrast to patients with parkinsonism, there is no concomitant cogwheel rigidity, freezing, or loss of postural reflexes. Classically, catatonia is a feature of schizophrenia, but it can also occur with severe depression. Gelenberg also stated that catatonia can appear with conversion hysteria, dissociative states, and organic brain disease. However, we think that the organic syndromes of akinetic mutism, abulia, encephalitis, and so forth should be distinguished from catatonia and catatonia should preferably be considered a psychiatric disorder.

Video 1.43 Catatonia.

Video 1.44A Another examples of catatonia.

Video 1.44B An example of a milder case of catatonia.

Depression is commonly associated with a general slowness of movement and of thought, so-called psychomotor retardation; catatonia can be considered an extreme case of this problem. Although depressed patients are widely recognized to manifest slowness in movement, some—particularly children—might not have the more classic symptoms of low mood, dysphoria, anorexia, insomnia, somatizations, and tearfulness. In this situation, slowness as a result of depression can be difficult to distinguish from the bradykinesia of parkinsonism. As in catatonia, lack of rigidity and preservation of postural reflexes may help differentiate psychomotor slowness from parkinsonism. However, there can be loss of facial expression and decreased blinking in both catatonia and depression. Lack of Myerson sign, snout reflex, and palmomental reflexes are the rule, all of which are usually present in parkinsonism. In children with psychomotor depression and motor slowness ( Video 1.45 ), the differential diagnosis is that of juvenile parkinsonism, including Wilson disease and the akinetic form of HD.

Video 1.45 Psychomotor slowness.

Some patients with obsessive-compulsive disorder (OCD) may present with extreme slowness of movement, so-called obsessional slowness ( Video 1.46 ). Hymas and colleagues (1991) evaluated 17 such patients out of 59 admitted to hospital with OCD. These patients had difficulty initiating goal-directed action and had many suppressive interruptions and perseverative behavior. Besides slowness, some patients had cogwheel rigidity, decreased arm swing when walking, decreased spontaneous movement, hypomimia, and flexed posture. However, there was no decrementing of either amplitude or speed with repetitive movements, no tremor, and no micrographia. In addition, there was no freezing or loss of postural reflexes. Like other cases of OCD, this is a chronic illness. Fluorodopa positron emission tomography scans revealed no abnormality of dopa uptake, thereby clearly distinguishing this disorder from PD ( ). However, there is hypermetabolism in orbital, frontal, premotor, and midfrontal cortex, suggesting excessive neural activity in these regions.

Video 1.46 Obsessional Slowness.