- Clinical signs
- Lesion localization
- Differential diagnosis
- Localized tremor syndromes
- Generalized Tremor Syndromes
- Intention tremors due to cerebellar disorders
Involuntary movement disorders result in some of the most dramatic clinical presentations in veterinary medicine. Classically, these disorders are present during periods of inactivity rather than during voluntary movement. Cerebellar disease, conversely, can result in apparent involuntary abnormalities during movement. Some involuntary movements are persistent while others are episodic. Certain involuntary movements have characteristics that allow for identification of specific causes, whereas others are only a reflection of dysfunction of the nervous or musculoskeletal systems. Clinically, it is important to first identify the type of involuntary movement present. Subsequently, a more directed approach can be used to establish the cause of the movement disorder.
Involuntary movement disorders are less well classified in animals than in humans. Terms such as tics, twitches, shivering, shuddering and fasciculation are often used to describe episodic, irregular muscle contractions. They are usually manifested through abnormal motion of the limbs, trunk or head. There are seven forms of involuntary movement.
Myoclonus is a shock-like contraction of a muscle or muscles that tends to occur repeatedly in a rhythmic pattern () and may persist during sleep. It is akin to the rhythmic depolarization and contraction that occurs in the heart with each beat. Myoclonus can be focal, multifocal or generalized. It often presents in the thoracic limbs, however, the pelvic limbs or the facial muscles (including the tongue) may also be involved. Myoclonus may be physiological such as that seen when falling asleep or during sleep), epileptic or symptomatic associated with central nerves system (CNS) disease. An idiopathic, essential myoclonus has been recognized in people but has not been described in veterinary medicine. Myoclonus in dogs is usually the result of distemper infection, which establishes a pacemaker-like depolarization of local motor neurons; however, it has been associated with lead toxicity and other causes of CNS inflammation.
Seizure activity also results in spontaneous involuntary movements. With generalized seizures, the clinical pattern is fairly characteristic including falling to a lateral recumbent position, rigidity and eventually paddling or gaiting movements of the limbs. With focal seizures, however, localized involuntary movements such as twitching of a single limb or part of the face may be present. Electroencephalography (EEG) must be performed at the time of the movement to confirm the cerebral aetiology of the disorder, but this is rarely practical in veterinary medicine. A detailed discussion of seizures can be found in site.
Tremor is one of the most common involuntary movement disorders in humans and is also surprisingly common as a clinical abnormality in dogs. Tremor is an involuntary, rhythmic, oscillating movement of fixed frequency resulting from alternate or synchronous contraction of reciprocally innervated antagonistic muscles (). It can be focal, affecting just one limb or the head for example, or generalized. Electromyographically, tremor is characterized by rhythmic bursts of motor neuron activity occurring in opposing muscle groups. The contraction of muscles with opposing function givestremora biphasic nature. This biphasic character differentiates tremor from other abnormalities of movement. While seen during the awake state, true tremor should cease with sleep. As for myoclonus, tremors may be physiological, idiopathic (or essential) such as that seen in senile tremor of dogs, or pathological due to a nervous system disease.
An intention tremor occurs or is worsened when the animal intends to perform a function in a goal-oriented manner. This type of tremor is usually most evident when the animal attempts to eat or drink. An intention tremor usually occurs at a frequency of between 2 and 6 times a second, and is most often associated with disease of the cerebellum. Other signs of cerebellar disease that accompany cerebellar tremor include ataxia (incoordination, swaying from side to side); dysmetria (‘goose-stepping’, overflexing of the limbs when walking); menace deficits (with normal vision and pupillary light reflexes); head tilt; nystagmus (); truncal sway; and infrequently anisocoria ().
Dyskinesia is defined as impairment of the power of voluntary movements resulting in fragmented or incomplete movements (). Dogs reported with these abnormalities may adopt abnormal postures, such as holding up a limb in an attempt to move or adopting a kyphotic posture of the spine without being able to initiate movement. The pathophysiological mechanisms underlying these movements are poorly understood, but may represent a central neurotransmitter or pathway abnormality or possibly a local muscular abnormality.
Myokymia and neuromyotonia
Myokymia and neuromyotonia refer to the involuntary rippling of muscles that persists even during sleep and under anaesthesia. These disorders represent a continuum of signs that result from motor axon or terminal hyperexcitability. This hyperexcitability can be caused by a wide variety of disorders of the CNS and peripheral nervous system (PNS) but is particularly related to changes in ion channel function. Electromyography (EMG) studies of myokymia reveal short bursts of ectopically generated motor unit potentials, firing at rates of 5-62 Hz and appearing as doublets, triplets or multiplets. These bursts fire rhythmically or semi-rhythmically and sound like soldiers marching. Neuromyotonia is characterized by muscle stiffness and persistent contraction related to underlying spontaneous repetitive firing of motor unit potentials. On EMG there are prolonged bursts of motor unit potentials, firing at rapid rates of 150-300 Hz, which begin and end abruptly, do not occur repetitively in a rhythmic fashion and have a characteristic waning amplitude. There are few descriptions in companion animals but it appears to be an emerging problem in Jack Russell Terriers.
This term describes prolonged and severe contraction of muscles that may be painful and can be either focal or generalized. Examples of diseases associated with cramps include ‘Scotty cramp’, ‘episodicfalling of Cavalier King Charles Spaniels’, and muscle cramps secondary to hypoadrenocorticism. As these are paroxysmal syndromes they are described in full in site.
Tremor is ultimately a disorder of movement (). Therefore, lesions in any region of the CNS, PNS and musculoskeletal system primarily responsible for normal movement, may generate a tremor. This makes localization challenging when considering the clinical signs alone (). In humans, important motor areas include the basal nuclei and other components of the extrapyramidal system, the cerebellum, diffuse neuronal cell bodies involved in segmental and supraspinal reflex mechanisms, components of the lower motor neuron (LMN) and the interconnecting pathways. Additionally, abnormalities of the mechanical apparatus of the limbs (e.g. bones, joints and tendons) may also result in tremor as a result of pain and weakness. However, species differences do exist and it is important to note that lesions involving the basal nuclei and substantia nigra commonly result in tremor in human beings but not in dogs ().
Tremors that occur or worsen when an animal is trying to perform purposeful movements (intention tremor) are most often associated with cerebellar disease. Fine tremor (decreased amplitude and increased frequency) is more often associated with diffuse neuronal disease or muscle weakness. The causative lesion may give rise to other signs of neurological dysfunction that can help to define the localization, such as dysmetria associated with cerebellar disease.
Several hypotheses have been proposed to explain physiological tremor. Traditionally it has been thought to represent the passive vibration of body tissues produced by mechanical activity of cardiac origin. However, of greater significance is probably the contribution of spontaneous firing of groups of motor neurons and the natural resonating frequencies of muscle fibres. Certain abnormal tremors, especially the metabolic variety of action tremors, due for example to hypoglycaemia and phaeochromocytoma, are believed to be exaggerations of physiological tremor.
The cerebellum functions to control movement once movement has been initiated (). The cerebellum also assists with regulation of posture, unconscious proprioception and muscle tone. Structurally, the cerebellum contains two lateral hemispheres primarily responsible for limb movements; a median portion or vermis, primarily responsible for regulating posture and muscle tone; and a ventral portion (the flocculonodular lobe), primarily responsible for the maintenance of equilibrium and coordination of head and eye movements (). The cerebellar cortex in all regions is made up of the outer molecular layer, the middle Purkinje cell layer and the inner granule cell layer (). The cerebellar cortex has a predominant inhibitory influence on the three paired cerebellar nuclei of the subcortical white matter (fastigial, interposital and dentate) that are then responsible for the control, but not the initiation, of head and limb movements. Afferent and efferent information to and from the cerebellum is transmitted via three paired cerebellar peduncles attaching the cerebellum to the brainstem.
Signs of dysfunction in any area of the cerebellum usually include abnormalities of the rate, range, direction and force of motor movements. There are no signs of weakness or paresis seen with ‘pure’ cerebellar dysfunction. Tremor seen with cerebellar disease is most obvious when the animal tries to make a goal-orientated effort and it is therefore referred to as an intention tremor. This type of tremor, which implies a lesion of the cerebellar hemispheres, often becomes more obvious when an animal attempts to lower its head to eat or drink, intention tremors may involve the head or the entire body, and may be accompanied by other signs of cerebellar dysfunction such as ataxia and hypermetria.
CNS and peripheral nerve dysfunction
A common underlying theme to the generation of tremors or other involuntary movements is spontaneous neuronal or axonal discharges in the CNS and/or PNS. This increased excitability can be caused by any disorder that interferes with normal myelination, ion channel function, electrolyte concentrations (especially potassium, calcium and sodium) and neurotransmission. Inherited (e.g. dysmyelination in Chow Chows and Weimaraners), inflammatory and compressive disorders can all affect any one or more of these parameters producing tremors or other involuntary movements.
The differential diagnosis is based upon the type of tremor or involuntary movement present. Tremors tend to be localized or generalized, and categorizing movement disorders in this way helps to determine the list of differential diagnoses () (). Intention tremor, being somewhat different, is most often associated with cerebellar diseases ().
Obtaining an accurate history of the patient is important to define the onset and progression of the condition in addition to elucidating any underlying systemic health problems that could be causing the disorder. Important questions are listed in Important questions to ask when establishing a diagnosis:
Important historical questions about the patient with tremors and involuntary movement disorders
- Was the onset of the condition acute?
- Has the condition been progressive?
- Has the condition been constant or intermittent?
- Do the tremors disappear during sleep?
- If the animal is young, is there any information available about the littermates?
- Is there any possibility of exposure to toxins?
- What medications is the patient on?
- Is the patient on a standard diet?
- Have there been any recent changes in personality or behaviour?
- Are there any recent changes with the patient’s appetite or thirst?
Complete physical examination is essential as some tremor disorders may be associated with systemic disease. Many tremor syndromes may also be associated with neurological deficits; therefore, a neurological examination can help to localize the causative lesion or associated deficits and determine the next stages necessary in the diagnostic work-up.
The following tests should be considered in most patients with tremors and movement disorders:
Haematology, serum biochemistry analysis and urinalysis can help rule out systemic disease including hypoglycaemia, hypocalcaemia and other electrolyte abnormalities
Testing for possible toxin exposure can be difficult without knowledge of which toxin to look for; serum cholinesterase activity can be dramatically lowered in cases of organophosphate toxicity; blood lead levels should be considered if there is a history of possible exposure
Thoracic and abdominal radiographs should be performed to rule out systemic neoplasia
Cerebrospinal fluid (CSF) analysis is necessary to rule out CNS inflammatory diseases
Serum and CSF serology can confirm the infectious nature of a CNS inflammatory disease
Advanced imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI) can help to rule out destructive inflammatory lesions in the CNS as well as focal mass lesions (e.g. neoplasia).