Parkinson Disease and Other Hypertonic–Hypokinetic Syndromes

The common feature of diseases of the basal ganglia is a movement disorder in which there is either too much or too little movement, that is, an excess or deficiency of movement impulse, movement automaticity, and/or muscle tone (see section ▶ 5.5.2).


In general, such diseases are characterized by the following:




  • Disturbances of the process or movement (always).



  • Abnormally increased or diminished muscle tone (usually).



  • Involuntary movements (often).



  • Associated neuropsychological manifestations (sometimes).




Increased muscle tone is often associated with paucity of movement, and, conversely, diminished muscle tone with excessive movement. Thus, there are two main classes of extrapyramidal syndrome:




  • Hypertonic–hypokinetic extrapyramidal syndromes (above all, parkinsonian syndromes and related neurodegenerative disorders, which will be discussed in this section).



  • Hypotonic-hyperkinetic extrapyramidal syndromes (e.g., chorea, athetosis, ballism, and dystonia, which will be discussed in the next section).


6.9.1 Overview




Note



In hypertonic–hyperkinetic syndromes, elevated muscle tone is typically manifest as rigidity. Paucity of movement, depending on its severity, is termed either hypokinesia (= diminished movement) or akinesia (= complete lack of movement). A third so-called “cardinal manifestation,” tremor, is also commonly present. This clinical triad, called the parkinsonian syndrome (or parkinsonism), is typically found in idiopathic Parkinson disease. Often, postural instability (= tendency to fall) occur as a fourth cardinal manifestation.


Parkinson disease, however, is only one possible cause of parkinsonism; there are many others besides. Parkinsonism may be due to an underlying illness or condition other than idiopathic Parkinson disease (symptomatic parkinsonian syndromes). In addition, several systemic neurodegenerative diseases cause parkinsonism. These rare diseases are marked by a loss of neurons not only in the basal ganglia, but also in other areas of the CNS, and thus are clinically characterized not only by extrapyramidal manifestations, but also by neurologic deficits localizable to other regions of the brain. The most important diseases in this category, multisystem atrophy (MSA) and corticobasal degeneration (CBD), will be discussed further in this chapter. Lewy body dementia belongs in this category as well but will be discussed later in the subsection on dementia (section ▶ 6.12).


6.9.2 Parkinson Disease (Idiopathic Parkinson Syndrome)


Definition Parkinson disease is defined by its clinical manifestations (characteristic body posture and gait, with hypokinesia, rigidity, and, usually, rest tremor) and their pathologic correlates in the brain: Lewy bodies containing α-synuclein and degeneration of dopaminergic neurons in the pars compacta of the substantia nigra (a pigmented nucleus in the midbrain).


Epidemiology, Etiology, and Pathogenesis


Epidemiology and etiology Parkinson disease has an overall prevalence of 0.15%. Its age-specific prevalence rises with increasing age, to 1% in persons older than 60 years and 3% in persons older than 80 years. Most cases are idiopathic, that is, without any identifiable cause.


Familial clustering of Parkinson disease is seen in 5 to 15% of cases (so-called hereditary Parkinson disease); patients who develop Parkinson disease at an unusually young age are particularly likely to have a problem of this type. To date, 18 genetic loci (PARK1 through PARK18) and at least 7 genes have been identified whose mutations can cause a hereditary parkinsonian syndrome. The mode of inheritance can be autosomal dominant with variable penetrance or autosomal recessive. A special type is the familial Parkinson–dementia complex seen on the island of Guam. The combination of parkinsonism and dementia also sometimes exhibits familial clustering.


Pathogenesis The neuropathologic hallmark of idiopathic Parkinson disease is degeneration of the dopaminergic neurons of the substantia nigra and the locus ceruleus. Hyaline inclusion bodies, called Lewy bodies, are found within the degenerated neurons. The loss of dopaminergic neurons leads to a degeneration of the (inhibitory) nigrostriatal dopaminergic pathway and, therefore, to dopamine deficiency in the striatum. This, in turn, leads to enhanced activity of the striatal glutamatergic neurons, which produces the clinical manifestations of the disease.




Additional Information



In the Braak system of Parkinson disease there are six neuropathologic stages that trace the temporal progression of intraneuronal Lewy body formation from lower to higher neural centers in the brain. In stages 1 and 2, before any clinical manifestations of the disease have arisen, Lewy bodies are present only in certain areas of the brainstem and the olfactory system. The first symptoms arise in stages 3 and 4 when Lewy bodies begin to appear in the substantia nigra. Finally, in stages 5 and 6, Lewy bodies are found in diffuse areas of the cerebral cortex.


Clinical Features


The clinical picture of idiopathic Parkinson disease and of hereditary parkinsonian syndromes ( ▶ Fig. 6.55) is typically characterized by:




  • Hypokinesia, i.e., slowing of movement.



  • Increased muscle tone (rigidity).



  • Abnormal body posture (stooped head and trunk, flexion at the knees).



  • Impaired postural reflexes, sometimes leading to falls.



  • Often tremor.



  • Later, neuropsychological deficits and certain vegetative/autonomic disturbances such as oily (seborrheic) face and bladder dysfunction.




Practical Tip



The motor signs are often only unilateral, or more marked on one side, when the disease first appears. They can be aggravated by emotional stress.



9783131364524_c006_f055.eps


Fig. 6.55 Parkinson disease. (a) Typical posture with stooped head and upper body and lightly flexed elbows, hips, and knees. (b) Hypomimia (paucity of facial expression) and the asymmetry of manifestations that is typical in idiopathic Parkinson disease (the right elbow is somewhat more strongly flexed than the left).


Hypokinesia Hypokinesia manifests itself as paucity of facial expression (mask-like facies), reduced frequency of blinking, and speech disturbances (dysphonia, i.e., slow, monotonous, unmodulated speech, and repetitions). There is little spontaneous movement, and the normal accessory movements (e.g., arm swing during walking) are diminished or absent. The patient’s handwriting becomes progressively smaller (micrographia). Repeated or alternating movements (e.g., finger-tapping) are performed slowly and with smaller excursions (dysdiadochokinesia; cf. ▶ Fig. 3.19). Axial movements, such as turning around while standing or turning over in bed, are difficult to perform. Very severe hypokinesia is sometimes called akinesia.


Gait A parkinsonian gait is characterized by a mildly stooped posture, with the head jutting forward, and a small-stepped, often shuffling gait, without accessory arm movements ( ▶ Fig. 6.56). To turn around while standing, the patient makes many small turning steps.



9783131364524_c006_f056.eps


Fig. 6.56 Typical parkinsonian posture while walking: inclined head, slightly stooped upper body, flexed elbows, and lightly flexed hips and knees.


Increased muscle tone This is primarily evident as rigidity ( ▶ Fig. 3.24), felt by the examiner during large-amplitude, passive flexion and extension of the joints. Rigidity is sometimes easier to detect when the patient voluntarily contracts the muscles on the opposite side of the body. Often, during passive movement, the examiner may feel a small, brief, periodically recurring diminution of muscle tone, known as the cogwheel phenomenon, which is usually most evident at the wrist ( ▶ Fig. 3.25). The patient’s postural tone, too, is elevated; if, for example, the head is lifted off the bed and let go, it may remain suspended in midair for some time (the Wartenberg sign; the classic literature spoke of a “coussin psychique,” i.e., a virtual pillow).




Practical Tip



Another test for the objectification of rigidity is the so-called swinging test: the examiner grasps and shakes the patient’s forearm back and forth. Rigidity markedly diminishes the swinging (pendular) motion of the wrist. The test can also be performed at the elbow or knee joint.


Tremor Three-quarters of patients with Parkinson disease have tremor sooner or later in the course of their disease, typically a distal rest tremor at a frequency of 5 Hz. A pronation–supination (“pill-rolling”) tremor is highly characteristic. The tremor is present at rest and generally disappears on voluntary movement; it is sometimes increased by mental exertion, deep concentration, or walking. Some patients have postural and intention tremor in addition to rest tremor (see ▶ Fig. 3.22).


The risk of falling An impairment of postural reflexes, combined with hypokinesia, has the consequence that changes of body posture and orientation in space can no longer be compensated for by reflexive, rapid corrective movements. The most obvious manifestations of this problem are pro- and retropulsion. If the patient is pushed while standing still, or stumbles over an obstacle, the movements made to regain balance are too small and too slow, and a fall may result.




Practical Tip



The patient’s postural reflexes and possible tendency to fall can be tested with the pull test and the push-and-release test. In the former, the examiner stands behind the patient and pulls back on both shoulders; in the latter, the patient is propped up in a standing position from behind by the examiner’s hands, which are then suddenly released. (Obviously, when performing these tests, the examiner must make sure that the patient can be caught in case of a fall.)


Impaired olfaction An impaired sense of smell is almost universal in patients with idiopathic Parkinson disease but rare in patients with symptomatic parkinsonism.


neuropsychological deficits When the first symptoms of Parkinson disease arise, the patient’s cognitive functions are generally normal or only mildly impaired. As the disease progresses, however, neuropsychological deficits almost always arise. Memory is impaired, cognitive processes are slowed (bradyphrenia), and there is a tendency toward perseveration. Rapid changes in thought content are difficult to achieve, and the planning and execution of actions and behaviors is impaired (so-called dysexecutive syndrome).


Psychiatric manifestations Depression affects one-third to one-half of all patients over the course of the disease and is treatable. Isolated apathy (without depression) can also arise. Impulse-control disorders, such as compulsive shopping, gambling, or hypersexuality, are usually side effects of dopaminergic drugs. The patient’s perceptions and thought processes can become abnormal over the course of the disease, because of either the disease itself or its dopaminergic treatment; hallucinations and overt psychoses can result.


Disturbances of autonomic and vegetative function Such disturbances arise partly as a by-product of hypokinesia and partly because of direct involvement of the autonomic nervous system. These include seborrhea (an oily face, caused by excessive fat production in the skin), hypersalivation, cold intolerance, a tendency toward orthostatic hypotension and constipation, urinary urgency (possibly causing incontinence), and sexual dysfunction (altered libido, erectile dysfunction). Insomnia and behavioral disturbances during REM sleep (see section ▶ 10.4) are often seen early on in the course of disease; the patient’s sleep can also be disturbed by restless legs syndrome (see section ▶ 10.2.2) or spontaneous pain in the limbs.


The nonmotor manifestations of Parkinson disease are summarized in ▶ Table 6.30.

















Table 6.30 Nonmotor manifestations of Parkinson disease

Autonomic/vegetative


Cognitive


Psychiatric




  • Hyperhidrosis



  • Hypersalivation



  • Seborrhea



  • Obstipation



  • Cold intolerance



  • Circulatory dysregulation, orthostatic hypotension



  • Sexual dysfunction (loss of libido, abnormally increased libido, erectile dysfunction)



  • REM-sleep behavioral disorder



  • Insomnia



  • Daytime somnolence, sleep attacks



  • Pain, paresthesiae



  • Hyposmia, anosmia




  • Slowed thinking (bradyphrenia)



  • Perseveration



  • Impaired planning, strategy, and execution (dysexecutive syndrome)



  • Cognitive impairment, ranging from mild to severe frontal dementia in advanced disease




  • Depression



  • Apathy



  • Hallucinations, illusions



  • Psychosis (mainly as a drug effect)



  • Impulse-control disorder (compulsive shopping, gambling, or sexual behavior; mainly as a drug effect)


Classification and grading of manifestations The manifestations described are present to variable extents in different patients with Parkinson disease. Generally speaking, the disease has three main clinical variants:




  • The akinetic-rigid type (without tremor).



  • The tremor-dominant type (with little hypokinesia and rigidity).



  • The mixed or “equivalence” type (with roughly equal severity of all three cardinal manifestations—rigidity, hypokinesia, and tremor).


Individual clinical manifestations can be graded on pseudoquantitative scales, if this is desired for long-term follow-up or for research purposes, for example, with the Webster Rating Scale ( ▶ Table 6.31) or the very detailed Unified Parkinson’s Disease Rating Scale (UPDRS), which is not reproduced here. Cognitive function can be assessed with the MOCA test or the Mini-Mental State Examination (MMSE; see ▶ Table 3.11).








































Table 6.31 Simplified scale for evaluating the severity of individual signs of Parkinson disease

1. Bradykinesia of hands, including handwriting


0 = normal


1 = mild slowing


2 = moderate slowing, handwriting severely impaired


3 = severe slowing


2. Rigidity


0 = none


1 = mild


2 = moderate


3 = severe, present despite medication


3. Posture


0 = normal


1 = mildly stooped


2 = arm flexion


3 = severely stooped; arm, hand, and knee flexion


4. Arm swing


0 = good bilaterally


1 = unilaterally impaired


2 = unilaterally absent


3 = bilaterally absent


5. Gait


0 = normal, turns without difficulty


1 = short steps, slow turn


2 = markedly shortened steps, both heels slap on floor


3 = shuffling steps, occasional freezing, very slow turn


6. Tremor


0 = none


1 = amplitude < 2.5 cm


2 = amplitude > 10 cm


3 = amplitude > 10 cm, constant, eating and writing impossible


7. Facial expression


0 = normal


1 = mild hypomimia


2 = marked hypomimia, lips open, marked drooling


3 = mask-like facies, mouth open, marked drooling


8. Seborrhea


0 = none


1 = increased sweating


2 = oily skin


3 = marked deposition on face


9. Speech


0 = normal


1 = reduced modulation, good volume


2 = monotonous, not modulated, incipient dysarthria, difficulty being understood


3 = marked difficulty being understood


10. Independence


0 = not impaired


1 = mildly impaired (dressing)


2 = needs help in critical situations, all activities markedly slowed


3 = cannot dress him- or herself, eat or walk unaided


Source: Webster DD. Critical analysis of the disability in Parkinson disease. Mod Treat 1968;5(2):257–282.


Note: The sum of the scores indicates the degree of severity of Parkinson disease: 0–10 mild, 10–20 moderate, 20–30: severe.


The Neurologic Examination and Other Diagnostic Tests




Note



The diagnosis of Parkinson disease is based on the typical clinical manifestations and characteristic findings on neurologic examination.


History Important points to be addressed in clinical history-taking include the following:




  • Has the patient had difficulty with fine motor activities such as writing, getting dressed, or eating?



  • Is the patient’s gait less steady than before, perhaps with stumbling or falls?



  • Has the patient noticed any difference between the right and left sides of the body?



  • Does the patient suffer from pain or disturbed sleep?



  • Has there been any impairment of the sense of smell or any difficulty swallowing?


Neurologic examination In addition to hypokinesia, rigidity, tremor, and propulsion/retropulsion, the examination generally reveals the following:




  • Weak convergence (movements to focus the eyes are slowed).



  • A persistent glabellar reflex (i.e., lack of habituation of the reflex after repeated glabellar tapping).



  • Saccadic ocular pursuit movements.



  • Impaired olfaction.


The intrinsic muscle reflexes are normal, however, as are all somatosensory modalities.


For numerical grading, see the preceding paragraphs and ▶ Table 6.31.


Imaging studies CT and MRI of the head reveal no abnormalities and are generally performed only to rule out competing diagnoses, for example, symptomatic parkinsonian syndromes. The loss of dopaminergic afferent input to the striatum can be demonstrated with positron emission tomography (PET) or single-photon emission computed tomography (SPECT) after the administration of 18fluorodopa ( ▶ Fig. 6.57). Cerebral ultrasonography can reveal early changes in the substantia nigra.



9783131364524_c006_f057.tif


Fig. 6.57 An 18F-DOPA-PET scan in a normal person (left, top and bottom) and in a patient with incipient Parkinson disease, worse on the left side of the body (right, top and bottom). The basal ganglia are seen in axial and coronal section (upper and lower rows of images, respectively). The patient with Parkinson disease has a more than 20% reduction in the activity of dopamine decarboxylase in the right putamen (particularly in its dorsal aspect), with relatively normal activity in the caudate nucleus. (Image provided courtesy of Dr. F. Jüngling, PET/CT-Zentrum NW-Schweiz, St. Claraspital, Basel, Switzerland.)




Note



Idiopathic Parkinson disease is always a diagnosis of exclusion, that is, all varieties of symptomatic parkinsonism must be ruled out before this diagnosis can be made.


Testing of olfaction Impairment of the sense of smell early on in the course of disease is supporting evidence for idiopathic or genetically triggered Parkinson disease. Smell is tested with small samples of various substances (coffee, etc.).


Genetic testing In young patients with a positive family history, genetic testing can help secure the diagnosis and enable a more accurate prognosis.


Treatment, complications, and prognosis Effective treatment alleviates the manifestations of the disease, moving the symptomatic progression curve to the right by some 3 to 5 years, but does not affect the disease process as such. The putative early neuroprotective effect of certain antiparkinsonian drugs has not yet been confirmed.


Pharmacotherapy The goal of drug therapy is to replace the missing dopamine in the striatum.


Dec 28, 2017 | Posted by in NEUROLOGY | Comments Off on Parkinson Disease and Other Hypertonic–Hypokinetic Syndromes
Premium Wordpress Themes by UFO Themes