Continuing Education Activity

Akinesia or "absent movement" is a clinical sign that could be indicative of a number of disorders, depending on the age group of the patient. The varied heterogeneous pathogenesis must be understood in order to correctly diagnose and manage the underlying disorder. This activity outlines the evaluation, and management of akinesia and highlights the role of the interprofessional team in improving care for patients with this condition.

Objectives:

• Identify the etiology of akinesia.
• Discuss the pathophysiology of akinesia.
• Outline the management depending on the etiology of akinesia.

Introduction

The term akinesia refers to the inability to perform a clinically perceivable movement. It can present as a delayed response, freezing mid-action, or even total abolition of movement. Akinesia occurs when movement is not perceived either because the amplitude of the movement is small or because the time taken to initiate the reaction is significantly increased. The former is often a consequence of severe bradykinesia, which is commonly mistakenly referred to as akinesia. This makes it difficult to differentiate between the two. In akinesia, there is failure of a rapid build-up of adequate power to initiate the movement.

Akinetic states are associated with numerous etiological causes, that vary with the age of the patient. In adults, akinesia can present alone or as sequelae of neurodegenerative disorders.[1][2] Findings of akinesia noticed antenatally or neonatally is associated with fetal akinesia syndrome.

Etiology

The causes of akinesia can be classified based on the age group of presentation.

1. Adult-onset akinesia has been associated with the following two causes:

• Pure isolated akinesia
• Late stages of disorders affecting the basal ganglia or frontal lobes
  • Progressive supranuclear palsy (PSP) (also known as Steele-Richardson-Olszewski syndrome)
  • Parkinson's disease (PD)
  • Multiple system atrophy
  • Normal-pressure hydrocephalus.[1]

2. The fetal akinetic syndrome (fetal arthrogryposis or Pena–Shokeir syndrome type 1), is a cause of intrauterine fetal death or rarely a live birth, related to diffuse contractures across the body (arthrogryposis) of the fetus and subsequently reduced movement, further leading to intrauterine growth restriction, short umbilical cord, and pulmonary hypoplasia.[3]

Epidemiology

It has been found that akinesia in clinically observed parkinsonism is more commonly associated with the motor variant of frontotemporal lobe dementia (FTLD), rather than PD related frontal degeneration. Around 30% of patients with clinically confirmed FTLD showed parkinsonian features, notably, rigidity or akinesia.[4] Acute akinesia is a relatively rare phenomenon and occurs in 0.3% of patients with PD, secondary to infectious pathology or other stressors.[5] 

In the pediatric population, akinesia is often associated with the fetal akinetic syndrome. This is associated with high intrauterine mortality. However, the incidence in live births is 1 in 3,000 cases, with over 320 genes implicated in its pathology.[6] It is more predominant in the Asian, European, and African populations.[7]

Pathophysiology

The pathogenesis of akinesia in adults broadly appears to stem from pallidonigroluysian degeneration that predominantly leads to freezing.[1] However, the specific pathology depends on the type of akinesia. In cases with pure akinesia with gait freezing without any other symptom or diagnosis of PD, it is most likely related to PSP. Evidence of degeneration in the subthalamic nuclei, globus pallidus, and substantia nigra are related to PSP.[8][9] 

In patients with PD, the principal cause of akinesia appears to be a dysfunction in phasic and tonic dopamine release. This is in contrast to resting tremors caused mainly due to a dysfunctional tonic phase of dopamine release.[10] Another theory suggests that the akinesia in PD patients is related to bilateral frontal involvement and is also accompanied by deteriorating mental states.[11]

Fetal akinesia has been associated with around 320 genetic variations that could all present with this syndrome. Pathologically speaking, the pathology is evident at all levels, including the brain, spinal cord, motor neuron, neuromuscular junction, and the muscle.[12]

History and Physical

In PD, the examination of a patient with akinesia would reveal freezing mid-movement, festination of both gait and speech, and repetitive upper limb movements.[1] This freezing is typically associated with exaggeration of symptoms with ambulation through narrow spaces like doorways.[13] This usually does not respond to antiparkinson medication.

In akinetic patients secondary to PSP, the rigidity is mainly axial rather than appendicular. The earliest manifestation occurs with recurrent falls, due to profound rigidity, but atypical manifestations like non-specific dizziness, generalized motor slowing, and personality change, could also be present. Slowing of vertical saccades is the most common eye movement manifestation, along with difficulty in down-gazing.[14]

Antenatally, a patient carrying a fetus with possible fetal akinesia can present with reduced fetal movement. Later in the pregnancy, the patient presents with polyhydramnios, evidenced by abnormally increased fundal height.

In a live birth with fetal akinesia syndrome, the following sequence is often observed as a result of a lack of fetal movement. 

• Fetal joint contractures
• Pulmonary hypoplasia
• Polyhydramnios
• Micrognathia

Evaluation

The determination of akinesia in a patient is mainly clinical and characterized by a delay or inability to react or execute a motor command. Quantitatively, reaction time studies are used to assess the degree of akinesia. It typically reveals a delay in simple reaction time, but a normal choice reaction time.[2]

The neuroimaging studies employed in the assessment of akinesia include:

• Magnetic resonance imaging (MRI)
• Functional MRI
• Single-photon emission computed tomography
• Positron emission tomography

In patients with akinesia-rigidity dominant PD, in comparison to a tremor-dominant variant, a higher global functional connective density (FCD) in the akinetic-rigid dominant variant is in the left inferior frontal gyrus, right middle frontal gyrus, right superior frontal gyrus along with a lower global FCD in the akinetic-rigid dominant left cerebellum anterior lobule.[15]

Pure akinesia with gait freezing, associated with PSP, has imaging findings showing significant cortical thinning in inferior bilateral frontal, left orbitofrontal, right anterior cingulate, bilateral insula, bilateral supramarginal, right angular and precunial, and bilateral temporal areas, often involving the parahippocampal and lingual gyri.[16] The MRI can show midbrain atrophy with the classic hummingbird sign or the morning glory sign with loss of the lateral convex margin of the tegmentum. Patients have diffuse Tau protein aggregates in the basal ganglia on histopathology.

The current imaging strategies do not give any information on the neurotransmitter type involved in the disorder's pathogenesis. Futuristic models are likely to conduct pharmacological imaging, complex behavioral tasks along with movement analysis techniques, allowing practitioners to quantify the akinesia.[15]

A presumptive diagnosis of fetal akinesia is made after obtaining a normal karyotype and excluding other conditions. Antenatal diagnosis can be carried out as early as 12 weeks of gestation after clinically presenting with reduced fetal movement, fetal edema, or fixed limb posturing, as observed on antenatal ultrasonography.[3]

Treatment / Management

Treatment of akinesia in adults revolves around controlling the progression of the underlying disease. The management of akinesia is symptomatic rather than curative.

• Drug therapy: In patients with PD, this mainly aims to modify/supplement the impaired dopamine release.
• Progressive resistance exercise is useful in improving symptoms of an improved static posturography, gait, and the general quality of living in patients with an akinetic rigid variant of PD.[17]
• Surgical therapy: The most studied surgical procedure aiding in the management of akinesia is deep brain stimulation, typically used to improve dopamine secretion and improve symptoms of tremors, akinesia, and rigidity.
• Other procedures performed in severe cases include thalamotomy, pallidotomy, neural implants, and electrical stimulation.

The treatment for fetal akinesia is supportive mainly due to a dismal prognosis in a live birth. Resuscitative measures are initially employed to combat pulmonary hypoplasia. Medications like sildenafil and iloprost to control raised pulmonary pressures are initially used. They can still be converted to a less life-sustaining comfort care approach after adequate discussions with the parents. Antimicrobials may be required. Prolonged parental nutrition is often needed in these patients due to malrotation of gut, short-gut syndrome, and impaired swallowing. Central nervous system anomalies like seizures and endocrine disorders like hypothyroidism need treatment with anticonvulsants and thyroid hormone replacements.[3]

Differential Diagnosis

Adult akinesia should be differentiated from:

1. Catatonia: These patients are predominantly apathetic and present with posturing rather than difficulty initiating movement.
2. Akinesia arrest reaction: This is typically intermittent in onset, associated with seizure activity on electroencephalogram.[11]

Live births with fetal akinesia syndrome should be differentiated from:

1. Osteogenesis imperfecta: This is typically associated with multiple fractures, not accompanied by contractures, unlike fetal akinesia syndrome. Other findings, like blue sclera, conductive deafness, and mild stunting, would make this diagnosis more likely.[18]
2. Potter's sequence: This is often associated with renal agenesis, but not with contractures.
3. Congenital myopathies: This is not frequently associated with intrauterine death, but is associated with gradually progressing muscle weakness. 
4. Congenital myasthenia gravis: An infant with congenital myasthenia would present with ptosis, poor crying and sucking reflex, and facial, bulbar, and generalized weakness.[19]
5. Maternal antibodies to fetal acetylcholine receptor: A history of myasthenia present in the mother, would make this a more likely diagnosis.
6. Metabolic disorders: Mucopolysaccharidosis III, glycosylation type 1A deficiency, phosphofructokinase deficiency (glycogenosis VII)
7. Trisomy 18: Other midline defects like holoprosencephaly, omphalocele, cleft lip/palate would also be present in this disorder.[3]

Prognosis

Adult-onset akinesia has no curative therapy, but symptomatic treatment can significantly alter the damage done to the quality of life in these patients. Although a mild variant of akinesia cannot directly lead to death, severe forms of akinetic crises can cause dysphagia, autonomic dysfunction, and aspiration, which can prove fatal.

Fetal akinesia syndrome has been primarily found to be lethal in utero, with 30% of fetuses being stillborn. The ultimate prognosis is dependent on the underlying cause. The majority of live-born infants usually die within the first month of life. This could warrant an offer for the late termination of pregnancy in countries that allow it.[3]

Complications

Fetal akinesia is often lethal within the first month of life. This is due to the many complications associated with this condition.

• Pulmonary complications: Pulmonary hypoplasia, pulmonary hypertension, aspiration pneumonia.
• Oropharyngeal dysfunction: This leads to aspiration and subsequent pneumonia.
• Neurological complications: Seizures and hypothalamic dysfunction.
• Gastrointestinal complications: Short gut syndrome and intestinal malrotation.
• Endocrine dysfunction: Hypothyroidism from hypothalamic dysfunction.[3]

Akinesia in adults can often present as an emergency, known as akinetic crises. Parkinsonian hyperpyrexia, neuroleptic-like malignant syndrome, acute akinesia, and malignant syndrome in parkinsonism are other terms used to describe these akinetic crises. This variant spectrum may vary from total akinesia with dysphagia, hyperthermia, dysautonomia, the increment of muscle enzymes, and alterations of mental status, to only, the inability or difficulty in initiating movement.[20]

Consultations

Consultations will be required from neurologist, movement disorder specialist, physical therapy and rehabilitation, and neurosurgeon.

Deterrence and Patient Education

Adult-onset akinesia creates many challenges for both the patient and the family. Since the supportive treatment like physiotherapy and exercise therapy is primarily motivation driven, it is essential to counsel and encourage patients to seek and diligently follow through with it, over a prolonged period. Of importance, is the underlying depressive episode in these patients. Adequate counseling and medication in clinically depressed patients, a condition not uncommon in Parkinson disease and Parkinson plus syndromes, cannot be stressed upon enough.

In parents with a live/stillbirth suggestive of fetal akinesia syndrome, fetal surveillance in subsequent pregnancies is essential. An in utero detection will allow for early termination as an option for the parents. The phenotypic condition is derived from various causes, making the recurrence risk calculation less precise. The stipulated recurrence risk lies anywhere between 0% to 25%.[3] Less life-sustaining comfort care approach after adequate discussions with the parents can be initiated.

Pearls and Other Issues

• Akinesia refers to the inability to perform a clinically perceivable movement
• It occurs because the time taken to initiate the reaction is significantly increased, preventing a rapid build-up of adequate power from starting the movement.
• Adult-onset akinesia can present as pure isolated akinesia or in late stages of disorders affecting the basal ganglia or frontal lobes.
• Fetal akinesia syndrome has been primarily found to be lethal in utero. However, the rate of disease in live births is 1 in 3000 cases.
• In parents with a live/stillbirth suggestive of fetal akinesia syndrome, fetal surveillance in subsequent pregnancies is essential.
• Akinesia in adults can often present as an emergency, known as akinetic crises, which include dysphagia, hyperthermia, dysautonomia, the increment of muscle enzymes, and alterations of mental status.
• The management of akinesia is supportive rather than curative.
• Progressive resistance exercise is useful in improving symptoms of an improved static posturography and gait in the akinetic rigid variant of Parkinson disese.

Enhancing Healthcare Team Outcomes

An interprofessional team is of utmost importance in providing the best possible outcome both physically and psychologically, for patients with akinesia and their family. While the diagnosis of adult-onset akinesia is dependent on the neurologist, fetal akinesia can be appreciated by an obstetrician and fetal medicine specialist. The rehabilitation of akinesia in adults is heavily dependent on self-motivation and requires regular counseling and psychological evaluation. On the other hand, the parents of a live-born with akinesis, with potentially lethal etiologies, must be counseled and supported when opting for comfort care. Surgeons of numerous disciplines and neonatologists play a role in providing structural and functional corrections in these patients.[3] 

The nurse and the pharmacist are responsible for dispensing the right medication and dosage. Finally, physiotherapists' role cannot be undermined in both fetal and adult akinesia as they contribute to significantly improving the quality of life in these patients.

Collaboration shared decision making, and communication is crucial for a good outcome. The interprofessional care must use an integrated care pathway using an evidence-based. The earlier signs and symptoms of a complication are identified, the better is the prognosis and outcome.