REVIEW: PROGRESS IN MEDICINE
Year : 2007 | Volume
: 10 | Issue : 1 | Page : 21--30
Akinetic rigid syndrome: An overview
Praveen Gupta, Madhuri Behari
Department of Neurology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029, India
Department of Neurology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
Akinetic-rigid syndromes can be caused by diverse etiologies. It is vital to separate idiopathic Parkinson«SQ»s disease from other neurodegenerative diseases and causes of secondary parkinsonism as it has significant therapeutic implications. However even specialists may misdiagnose nonidiopathic parkinsonism as Parkinson«SQ»s disease in a quarter of cases. Often the history may be nonspecific and all investigations may be normal. The diagnosis may thus rest entirely on clinical features. The etiological diagnosis of Akinetic rigid syndrome has critical therapeutic and prognostic implications. Therefore we will review the various etiologies of akinetic rigid syndrome and highlight critical clinical features to aid in differential diagnosis.
|How to cite this article:|
Gupta P, Behari M. Akinetic rigid syndrome: An overview.Ann Indian Acad Neurol 2007;10:21-30
|How to cite this URL:|
Gupta P, Behari M. Akinetic rigid syndrome: An overview. Ann Indian Acad Neurol [serial online] 2007 [cited 2020 May 30 ];10:21-30
Available from: http://www.annalsofian.org/text.asp?2007/10/1/21/31481
Akinetic rigid syndrome implies slowness of initiation of movement specially involving upper body (akinesia) and rigidity characterized by abnormal stiffness due to increase in tone of both the agonist and antagonist muscles (lead pipe) or cogwheel rigidity, due to superimposed or underlying tremor. It may additionally be accompanied by slowness of movement (bradykinesia) and thought (bradyphrenia), difficulty initiating movement, progressive fatiguing and diminishing amplitude of repetitive alternating movements with or without tremor at rest, (usually 3-5 Hz) and on posture (usually 4-8 Hz) and postural instability. This symptom complex usually localizes the pathology to the extrapyramidal system. However this lack of movement should not be completely explained by diminished alertness, weakness, pain or contractures and psychological affliction. However at times the history may be vague with complaints of fatigue, pain, poor dexterity and cramps, making the diagnosis difficult. Non availability of proper history due to impaired cognition may further make matters difficult. Clues to etiology, like drugs and trauma come from history alone. The confirmatory diagnosis is by clinical examination alone as in the case of Parkinson's disease in which all tests are normal.
Parkinsonism can be caused by diverse etiologies. The fact that 25% cases diagnosed as idiopathic PD by specialist were incorrect on autopsy underscores the need for through clinical evaluation. The etiological diagnosis of akinetic rigid syndrome has critical therapeutic and prognostic implications. We will now review salient diagnostic features of various akinetic rigid syndromes by etiology.
In patients above 40 years of age neurodegenerative disease is the commonest etiology of akinetic rigid syndrome. In this group idiopathic Parkinson's disease (PD) needs to be differentiated from other syndromes as it carries a better prognosis. These diseases are slowly progressive and have characteristic extra pyramidal signs, progression and associated neurological involvement. The differential diagnosis may be considered depending on whether the disease is symmetrical [multiple system atrophy (MSA), progressive supranuclear palsy (PSP)] or asymmetrical [Parkinson's disease (PD), corticobasalganglionic degeneration (CBD)]
Asymmetrical Neurodegenerative Diseases
Idiopathic Parkinson's disease is characterized by insidious onset akinesia and rigidity (either lead pipe or cogwheel), generally involving one limb at onset, which involves axial musculature and becomes bilateral over two to five years with persistent asymmetry. Clinical asymmetry is retained as the disease progresses over 10 or more years.
Akinesia or bradykinesia
Fifty per cent of IPD patients complain of slowing up at presentation. The slowness of IPD involves both initiation and execution of movements, particularly sequential and volitional actions. Writing becomes smaller (micrographia). Gradually they develop difficulty washing, feeding, dressing and turning in bed, but these functions are rarely affected at presentation. Loss of facial expression occurs early, while decreased eye blinking, hypophonia and impaired swallowing leading to sialorrhoea are later features. Characteristically the patient will perform finger-thumb opposition movements well a few times and then the amplitude will diminish and motor arrest may occur. Limb bradykinesia generally responds well to dopaminergic agents.
The patient may historically complain of muscular aching and stiffness of limbs and back on account of rigidity. The rigidity of IPD is, constant throughout a full range of passive movement and therefore is called lead pipe rigidity. If a postural tremor is superimposed it takes on a ratchet characteristic described as "cogwheel" rigidity. The majority of patients have rigidity on examination, especially if synkinesis of the opposite limb is performed; the increased tone is often unilateral at presentation spreading to become bilateral over three to five years, but maintaining an asymmetrical emphasis. The rigidity initially targets limbs and later spreads axially predominantly involving limb and trunk flexors leading to characteristic stooped posturing with trunk, neck and arm flexion and foot inversion. The rigidity is abolished by sleep and in 80% of cases responds well to dopaminergic agents.
About 40% of patients will complain of tremulousness of hand at rest, which improves with action and 80% will have an asymmetrical 3-5 Hz rest tremor evident on examination.Asking the patient to relax, close their eyes and count down from 100 or making them walk with their arms hanging freely may bring out this tremor, if not present. A 4-8 Hz postural tremor is as frequent as the characteristic rest tremor. The tremor of IPD can affect the eyelids, jaw, chin and legs in addition to arms. Parkinsonian tremor is not associated with in coordination, is increased by anxiety and abolished by sleep. Limb activity attenuates rest but increases postural tremor.
IPD presenting as an isolated postural tremor, can be differentiated from essential tremor by its late onset, starting in one limb and a latency of a few seconds when the arm is extended. Also the breakthrough "rest" component of severe essential tremor can be discriminated from the rest tremor of IPD as its amplitude is reduced and the frequency is similar to that of the postural component. In IPD, the rest tremor has a higher amplitude and lower frequency than the postural component. 
Around 50% of rest tremors respond well to dopaminergic and anticholinergic agents, though rarely completely and a minority are refractory. Postural tremors of IPD, like essential tremor, may respond to both β blockers and ethanol.
Gait and postural reflexes
The patient usually complains of reduced speed of walking with shortening of steps, occasionally dragging of one leg. Reduced arm swing on the affected side is usually evident. Later a tendency to shuffle develops, followed by gait initiation difficulties, freezing and festination (involuntary acceleration while walking). They also have difficulties in turning and rising from a chair. While early slowing of gait responds to dopaminergic agents the later complications do not, though they may be helped by the presence of external cues-such as walking across lines or listening to a metronome ticking or marching music on a walkman tape.
Ocular movements especially pursuits and reflexive saccades are preserved till late unlike progressive supranuclear palsy. However formal testing of remembered saccades to an occluded target or anti-saccades reveals slowing.  A frank supranucleargaze problem is rarely seen. Restricted voluntary up gaze and convergence can, however, be seen and, indeed, is present in a minority of elderly normal subjects.
Younger onset IPD cases (including genetic Parkinson's disease associated with parkin mutations) are particularly prone to exhibit limb dystonia. This can be early morning or wearing off dystonia with a predilection for painful foot inversion, but can also manifest as a variety of segmental syndromes. Levodopa and dopamine agonists may worsen rather than improve dystonia in some of these young onset IPD cases and anticholinergic treatment or amantadine can be helpful.
PD patients frequently admit to impotence and have slowed bowel motility with associated constipation and abdominal pain. Symptomatic orthostatic hypotension may develop as the disease progresses and dopaminergic treatment is instituted however unlike multiple system atrophy it is not early feature. Urinary hesitancy may reflect IPD or prostatism, but urgency and incontinence are usually caused by bladder instability. Increased sweating "seborrhoea" and facial flushing are late disease features. Dopaminergic agents are ineffective and worsen hypotension. Anticholinergic drugs such as tolterodine worsen constipation but can help bladder instability. Constipation may respond to senna laxatives or lactulose.
Frank dementia is unusual at presentation though slowness with executive functions such as sorting, fluency and problem solving can be evident. Later, significant subcortical dementia occurs in 25% of the patients. Associated Alzheimer's disease may give rise to a dementia with cortical features and Diffuse Lewy Body disease is differentiated by characteristic fluctuating confusion, visual hallucinations and paranoid delusions. Dopaminergic and anticholinergic agents are ineffective and indeed may cause or exacerbate confusion, hallucinations and psychosis. Anticholinesterase inhibitors such as rivastigmine may be helpful. Mild apathy and frustration are common at disease onset and a majority of IPD patients are mildly depressed, though severe depression requiring antidepressant treatment is less common. Panic attacks and anxiety can be presenting features of IPD.
The akinetic rigid state of IPD is characteristically levodopa/dopa agonist responsive provided adequate drug is taken for at least a few weeks by the patient. A patient should not be labeled dopamine unresponsive on the basis of L-dopa challenge test.
Diffuse Lewy Body Disease
Diffuse Lewy body disease presents with an akinetic rigid state in around 24-40% patients., Approximately 90% will develop akinetic rigid syndrome in the course of illness. The other features are hypophonic speech, masked facies, stooped posture and festinating gait. These akinetic rigid features are responsive to levodopa simulating idiopathic PD., However rest tremor is uncommon in DLBD.,, Myoclonus may be present in 18% patients in contrast to PD. There is presence of syncope, repeated falls and neuroleptic sensitivity in this disease., However DLBD is characterized by presence of cognitive deficits within a year of diagnosis as opposed to PD and after Alzheimer's disease, it is the second most frequent cause of dementia., The cognitive deficits in DLBD are fronto subcortical in nature involving psychomotor speed, verbal fluency, problem solving and visuospatial abilities as opposed to early involvement of language and memory functions in Alzheimer's disease. The dementia in DLBD is associated with prominent visual hallucinations and a fluctuating mental state. The visual hallucinations are of well-formed, detailed animate figures evoking emotional responses. Systemized delusions are also common. Depression may be present in 50-60% of the patients. REM sleep behavior disorders are also frequent in this disease though they are not specific for it. According to a study comparing pathologically confirmed PD with DLBD, DLBD had older age of onset (68 vs 62), shorter disease duration, less frequent rest tremor (55% vs 85%) and response to levodopa is less frequent (70% vs 100%). The most useful feature may the predominant signs at presentation as DLBD presents with cognitive and psychiatric signs in 72% cases as compared to PD (6%).
Corticobasal degeneration (CBD) is strikingly asymmetrical in its presentation, mimicking IPD. Also, unlike other akinetic rigid syndromes, there is striking apraxia of the affected limb and the patient complains that the limb does not behave itself or follow orders and that it feels as if it belongs to somebody else. Patients have difficulty recognizing objects in their pockets or hands by tactile impressions alone due to cortical sensory loss with simultagnosia and dysgraphaesthesia, despite preservation of light touch and pin prick sensation. In extreme cases the patient may develop an alien limb-that is, the arm may involuntarily perform apparently purposeful movements like interfering in brushing of teeth with the other arm or opening door handles. An alien limb should not be confused with simple involuntary limb elevation which often reflects impaired cortical sensory processing rather than aberrant higher motor control.
The other manifestations in CBD include limb myoclonus that may be stimulus sensitive, asymmetric postural limb tremor, limb dystonia (may result in ulceration of the palm caused by involuntary finger flexion) with early and severe dysphagia and dysarthria Supranuclear gaze difficulties have been described with CBD, however they are less common than PSP. Patients may develop pyramidal signs such as extensor plantar responses. Cerebellar signs and dysautonomia are not typically seen in CBD as opposed to MSA.
Dementia is usually a late feature of CBD, but an early frontal dementia disease can occasionally be seen. Dysphasia occurs early and frequently and the patient may become anarthric making cognition difficult to assess. Frontal release signs can occasionally be seen. Cases with atypical presentation simulating fronto temporal dementia and primary progressive aphasia have also been described.
A poor levodopa response is invariable in this disorder and amantadine, in my experience, is also usually ineffective. Treatment is essentially supportive.,
Thus the main features that differentiate CBD from PD are ideomotor apraxia, alien hand, limb dystonia, cortical sensory loss, lack of gait difficulties and lack of response to levodopa.
Symmetrical Neurodegenerative Diseases
Multiple system atrophy
Multiple system atrophy most commonly begins in the early 50s and, unlike Parkinson's disease, it shortens life considerably, with a median survival of 9.3 years. However, there is a wide range both for age at onset and for survival. Parkinsonism occurs in 90% of patients with multiple system atrophy and is usually symmetrical unlike IPD. Cerebellar or pyramidal signs each occur in about half of the patients. Rest tremor is seen in MSA but is far less frequent than in IPD. Further limb ataxia or intention tremor can be present in MSA, particularly in later stages, which is never seen in IPD.
Autonomic dysfunction failure occurs in virtually all patients and it may precede the motor disturbance by months or even some years. In men, impotence is often the first symptom and incontinence, more than retention, is common in both sexes. Symptomatic postural hypotension is common and unlike PD occurs early and before dopaminergic therapy is instituted. Respiratory stridor affects about 30% of patients at some stage and when combined with parkinsonism is highly suggestive of multiple system atrophy. Severe apnoeic attacks and hypoventilation can become severe enough to warrant a tracheostomy. Speech may differ qualitatively from the hypophonic monotony of Parkinson's disease, incorporating quivering, strained or slurring components. Many patients develop severe aphonia, anarthria and dysphagia, which are rare in Parkinson's disease.
Unlike PD extraocular smooth pursuit movements are hypometric to pursuit with saccadic intrusion and may also show sustained nystagmus. Square wave jerks may also be evident on central fixation. Voluntary saccades are usually full and supranuclear gaze problems are noted occasionally.
Hyper reflexia in conjunction with spasticity and a positive Babinski response is only seen in MSA and not IPD.
The flexed posture of MSA patients can be extreme and unlike patients of IPD they become bent double with their chins on their chest. Limb dystonia can also be a feature of MSA.
While frontal executive problems are found in MSA, frank dementiais are rare, as are the hallucinations, confusion and psychosis associated with cortical Lewy body disease.,
MSA patients show a poor levodopa response. However, it can be good or excellent in 25% of patients, but this is usually transient. Still levodopa responses cannot be used to exclude a diagnosis of MSA. Levodopa induced dyskinesias in multiple system atrophy maybe absent or, when present, take the form of predominantly dystonic movements affecting the face and neck more than the limbs.,
Autonomic function tests can document disturbed control of blood pressure and heart rate, but taken in isolation they are not particularly helpful in determining whether this is due to multiple system atrophy or due to Parkinson's disease, as similar results can be obtained in both diseases. In contrast, an abnormal external sphincter electromyogram reflecting loss of anterior horn cells in Onuf's nucleus in the sacral cord is highly suggestive of multiple system atrophy in the appropriate clinical setting. The presence of putaminal hypo intensity relative to globus pallidus on 1.5 tesla T2 weighted MRI or slit hyper intensity of the lateral putaminal margin, with or without cerebellar and putaminal atrophy may suggest MSA., In a study MRI showed, a hyper intense rim at the lateral edge of the dorsolateral putamen in 34.5% of cases and a 'hot cross bun' sign in the pontine basis (PB) in 63.3%. However neuro imaging may entirely be normal. It is useful to remember that a non-demented patient who is impotent and incontinent with poorly responsive parkinsonism, pyramidal and cerebellar signs does not have another single alternative diagnosis.
Progressive Supranuclear Palsy (Steele-Richardson-Olszewski Syndrome)
Progressive supranuclear palsy (PSP) presents as a symmetrical rather than asymmetrical Akinetic rigid syndrome in contrast to IPD. Still it is commonly misdiagnosed as PD. The median age of onset is 55-70 years. It involves the trunk and neck rather than the limbs, causing early postural and gait instability with falls and a dystonic posture where the trunk is flexed but the neck extended. Any elderly patient with truncal or neck rigidity either in the absence of or with only mild limb involvement and impaired postural reflexes leading to backward falls should be suspected of having PSP., Later, limb rigidity and brady kinesia develop in a symmetrical fashion but rest tremor is uncommon.,, Hyper reflexia and extensor plantars are findings, but the presence of associated cervical spondylosis can complicate the interpretation of such signs.,,
Voluntary gaze problems are pathognomonic but may be a late feature or even absent. PSP accounts for 75% cases of palsies of supra nuclear gaze., Difficulty with reading because of problems scanning the printed text may be a presenting feature., Impaired volitional saccades maybe brought out by asking the patient to look up and down voluntarily or left and right, in the absence of a target., This failure of voluntary down or lateral gaze corrects when the patient's eyes are centrally fixated and their head passively tilted backwards or rotated., Reflex saccades and pursuit eye movements (become slow with saccadic intrusions) are impaired at a later stage. Later nystagmus and frank oculoparesis may occur causing the patient to complain of diplopia. Square wave jerk on central fixation become evident.,, In PSP the optokinetic reflex is lost early with a sustained deviation of the eyes rather than saccades occurring on viewing a striped rotating drum., The combination of neck extension and a down gaze palsy predisposes PSP patients to falls, particularly when descending stairs. It also leads to the "sloppy tie sign" as the patient cannot look down to keep food from his plate on his fork while conveying it up to his mouth and so drops it on his tie.,, Also a staring expression maybe caused by eyelid retraction. This characteristic pattern of involvement differentiates it from IPD where ocular movements are initially spared.,
The bulbar involvement is early with initially a nasal spastic dysarthria (leads to growling and groaning) and hypophonia, followed by dysphagia.,
Urinary urgency, urge incontinence and constipation are frequently present, though postural hypotension is rare.,
Cognitive impairment in PSP mostly involves frontal lobe functions., Depression and frontal lobe impairments occur early in the disease. Memory, language and praxis deficits are seen later in the disease. Perseveration may be particularly obvious in speech, with repetition of syllables and words (palilalia) or even of whole phrases (palilogia). However the presence of severe dysarthria, hypophonia can make language assessment difficult and akinetic rigid state can mask apraxia. Limb apraxia is generally symmetrical and patients show difficulties imitating postures (ideomotor apraxia) and pantomiming patterns of limb movements (ideational apraxia). Eyelid opening apraxia can occasionally be present, patients taking seconds or even minutes to open their eyes volitionally after eye closure. Personality changes are common in PSP and emotional lability can cause patients to oscillate inappropriately between episodes of laughing and crying. In end stage of the disease grasp and pout reflexes can be elicited.
A poor levodopa response is usual though high doses can be beneficial initially. As with MSA, amantadine can be useful where levodopa is ineffective or poorly tolerated.,
Cerebrovascular disease is an important cause of an apparent akinetic rigid syndrome in the elderly and responsible for 3-6% of cases of parkinsonism., An extra pyramidal syndrome characterized by lower body parkinsonism may occur as a complication of cerebro vascular disease, even in the absence of recognized strokes. These patients are generally elderly and often hypertensive., The gait is short-stepped but often wide-based unlike PD and postural stability may be impaired., Start hesitation and freezing may occur, as in Parkinson's disease, but above the waist there is a striking absence of true parkinsonism. Thus, the voice and facial expression are lively and well modulated, the arms are used freely in spontaneous gesture, rest tremor is absent, there is no fatigue or decrement of alternating movements and the posture is usually upright., An acute onset, more rapid or stepwise progression, presence of multiple vascular risk factors and absence of sustained response to levodopa therapy are useful differentiating features from Parkinson' disease.,
Imaging often shows basal ganglia lacunae or white matter change, but sometimes hydrocephalus or, rarely cerebral tumor can give rise to a broadly similar picture.,
However it is important to recognize that people with Parkinson's disease can have concomitant cerebro vascular disease., This may sometimes be the cause of disproportionate and atypical walking and balance problems in someone who also has relatively mild classic upper body parkinsonism or it may cause a relatively abrupt onset of gait difficulty with falls in an elderly subject with a long history of typical Parkinson's disease., Computed tomography or magnetic resonance imaging may be useful in this context. In case of doubt over whether the patient has arteriosclerotic pseudoparkinsonism, Parkinson's disease or arteriosclerotic pseudoparkinsonism plus Parkinson's disease, an adequate trial of levodopa should be instituted.
Hereditary Causes of Akinetic Rigid Syndrome
Diseases with Akinetic rigid syndrome as a major component
Dopa responsive dystonia (DYT5) usually presents in childhood and adolescence with foot dystonia, diurnal fluctuations and frequent falls. These patients are exquisitely responsive to small doses of levodopa and do not develop motor fluctuations even in advanced disease. An akinetic rigid syndrome usually develops in later stages. Rapid onset dystonia parkinsonism is a rare autosomal dominant disorder with acute -subacute onset over hours to weeks. The typical symptoms are combined dystonia, levodopa unresponsive parkinsonism, greater bulbar and arm involvement as compared to legs. X-linked dystonia parkinsonism (Lubag's disease) has been described in middle-aged patients from Philippines. Dementia-parkinsonism -amyotrophy complex is an autosomal dominant disorder characterized by frontal lobe type of behavior disorder, cognitive impairment and amyotrophy.
Hereditary Disease with Akinetic Rigid Syndrome as Minor Component
Wilson's disease (WD)
In children and young adults WD is an important cause of akinetic rigid syndrome because if recognized timely it is eminently treatable and untreated it is invariably fatal. It is an autosomal recessive disorder of copper metabolism due to defect excretion of copper by liver. The patients with neurological WD present in second or third decade. It typically presents with dystonia, rigidity, tremor, bradykinesia, drooling, dysarthria, dysphagia, ataxia, unsteady gait and mental deterioration. There may be characteristic wing beating tremor, though all categories of parkinsonian tremors are seen. Bradykinesia is seen in 45% patients. Dystonia characteristically causes fixed sardonic smile and abnormal fixed limb postures., Common neuropsychiatric disorders are depression, lethargy, nightmares, dis-inhibited behavior and a schizophreniform illness with 20% of patients having onset with neuropsychiatric symptoms., An impairment of cognition is seen in 71% patients. A pathognamonic KF ring is seen in about 98% of neurological WD. Diagnosis is confirmed by the presence of characteristic T2W hyperintensity with central hypointensity in the basal ganglia, thalamus and sub-cortical white matter, elevated serum and urine copper levels and rarely a liver biopsy may be required. Wilson's disease should be suspected in any patient with akinetic rigid syndrome starting before 50 years with a combination of dystonia, bulbar dysfunction and neuropsychiatric symptoms and positive KF ring.
Huntington's disease (HD)
HD is a autosomal dominant disorder of trinucleotide repeats characterized by chorea, behavior changes and cognitive impairment. However HD often in patients younger than 20 years and rarely in adults (Westphal variant) may present as an Akinetic rigid syndrome with dystonia. Even in atypical HD in late stages akinesia and rigidity may be the dominant features. Additionally impairment of sustained voluntary movements, motor restlessness, gait abnormalities, abnormal saccadic eye movements and signs of bulbar dysfunction dysphagia and dysarthria may be seen in this disease., As many as 33% of rigid HD patients may show response to Levodopa. Seizures and myoclonus may also occur in this disease. Among the cognitive deficits an impairment of judgment organization, visuospatial functions, working memory, shifting sets and tracking multiple things together is seen early in the disease. The major affective disorder is the most common psychiatric problem seen in HD and depression may antedate other neurological signs by years. Neuroimaging may reveal atrophy of the caudate and genetic testing for trinucleotide repeats is diagnostic. Thus in an appropriate setting of family history (even without family history) specially in patients younger than 20, even without cognitive impairment HD may be strong diagnostic possibility in a patient presenting with Akinetic rigid syndrome.
Among other diseases dentatorubral pallidoluysian atrophy (DRPLA), Hallervorden Spatz disease, spinocerebeller ataxia (SCA) 2,3,6 and 17 and neuroacanthocytosis may present with or develop Akinetic rigid syndrome in the disease course.,,,,
Secondary Akinetic Rigid Syndromes
Akinetic rigid syndromes caused by drugs are important as they are common, iatrogenic and may be treated by withdrawal of offending drug. Clues that suggest a drug-induced state include: a) subacute, bilateral onset and progression of symptoms, b) early presence of postural tremor, c) concurrent dyskinesias of axial region especially of head and mouth, d) temporal relationship of occurrence with drug use and improvement with withdrawal.
Drugs that deplete presynaptic dopamine stores (reserpine or tetrabenazine) or block dopamine receptors such as phenothiazines (chlorpromazine), butyrophenones (haloperidol), thioxanthines (flupenthixol) and substituted benzamides (sulpiride) are commonly implicated. Neuroleptics cause parkinsonian symptoms with clinical signs in 20-40% patients. Advanced age, female gender and genetic susceptibility increase the likelihood of neuroleptic induced parkinsonism., Neuroleptic drugs can cause idiopathic, reversible, acute dystonic reactions with an incidence of 2% to 10%. Drug induced parkinsonism often resolves rapidly within days or weeks of discontinuing the offending drug, but after depot neuroleptic preparations it can take up to a year to subside. Recovery in adults may be incomplete. Withdrawal of offending agent is the first line of treatment. Drugs known to cause akinetic rigid states have been listed in the [Table 1].
A large number of toxins are implicated in causation of Akinetic rigid syndrome [Table 2]. So a careful history of environmental and occupational exposure along with drug abuse is necessary. MPTP+ induced parkinsonism discovered after an outbreak of akinetic rigid state in meperidine abusers, is rarely encountered in clinical practice. Akinetic rigid syndrome is commonly seen in miners and industrial workers exposed to heavy metals, especially manganese leading to slow movements, progressing to rigidity, dystonia, hyperreflexia, extensor plantar responses, cock up gait, postural and gait instability and postural tremor. Cyanide intoxication may also result in delayed parkinsonian symptoms and dystonia. Survivors of carbon monoxide poisoning, often develop delayed parkinsonism with dystonia after six weeks. Seventy-five per cent of such patients will recover within a year. Methanol and rarely ethanol intoxication can result in acute akinetic rigid syndrome with dystonia and blindness which stabilize and improve with time., Organic mercury poisoning causes neuronal loss and gliosis, resulting in parkinsonism associated with visual loss, ataxia, paraesthesias and cognitive dysfunction.
A list of toxins causing Parkinsonism is given in [Table 2]
Metabolic and autoimmune
Patients with acquired liver disease may present with insidious onset rapidly progressive symmetric parkinsonism similar to Wilson's disease. These patients have early gait and postural impairment and focal dystonia of face (50%). Cognitive and neuropsychiatric involvement is uncommon. Postural tremor is more prominent than resting tremor. MRI shows striking hyperintensities on T1-weighted images typically involving the substantia nigra and the globus pallidus. Patients with basal ganglia calcification may cause signs of akinetic rigid syndrome. Tetany due to hypocalcemia may be mistaken for an akinetic rigid syndrome. Hypothyroidism can cause lethargy, swelling and generalized lack of movement and may mimic parkinsonism. Hashimoto's encephalopathy and extrapontine demyelination may also cause akinetic rigid syndrome. Patients may develop a nonprogressive akinetic-rigid syndrome between one week and 12 months after cardiac arrest, hypotension or anesthesia. Though chorea is common, parkinsonism rarely occurs in autoimmune and collagen vascular diseases. Some cases associated with small cell carcinoma of lung and antiphospholipid syndrome are described., These causes are diagnosed by associated neurological and systemic symptoms.
Infections and post-infectious Akinetic rigid syndromes
Meningitis and encephalitis caused by viral, bacterial and fungal infections of the brain have been associated with parkinsonism, dystonia, choreoathetosis and ballismus. Transient movement abnormalities usually develop during the acute phase of illness. The classical encephalitis lethargica is no more seen. It was seen in epidemic in 1920s and was characterized by parkinsonism altered sleep cycle, occulogyric crisis, gaze palsies, dystonia, myoclonus, cognitive impairment, corticospinal signs and respiratory disturbances. Patients with AIDS dementia complex may rarely present as parkinsonism. Subacute sclerosing panencephalitis may present as Akinetic rigid state in late stages however age, typical stimulus sensitive myoclonus and cognitive decline help in clinching the diagnosis. Japanese encephalitis may present with acute onset akinetic rigid state along with unconsciousness and seizures. It may result in long-term extrapyramidal squealae. Akinetic rigid syndromes may occur as a part of post infectious encephalomyelitis in children. Mycoplasma pneumoniae , affects the CNS in 2% to 7% of cases especially in children and cause striatal necrosis manifested as dystonia, parkinsonism or both. Tubercular or pyogenic meningitis may cause basal ganglia infarcts due to vasculitis and present with hemiparkinsonism as sequelae. Cerebral fungal infections like Cryptococcus may lead to parkinsonism due to primary involvement of basal ganglia by cryptoccocomas or vasculitis., Toxoplasma abscesses in the basal ganglia may cause parkinsonism. Creutzfeld Jacob disease, Kuru and Gerstmenn Strauss Strinkler disease may be associated with parkinsonism. A list of infections causing akinetic rigid syndrome is given in [Table 3]
Trauma as a risk factor for delayed parkinsonism has a minor association at best., However traumatic strategically placed lesions can cause parkinsonism and should be considered when there is close temporal association and lesion is substantiated on imaging. Three patients with posttraumatic substansia nigra lesions presenting with parkinsonism one to five months after injury have been described. An akinetic rigid syndrome, dementia pugulistica has been described after repeated head injury in boxers. Usually these patients have concomitant cognitive, cerebellar and corticospinal signs and symptoms. Though rare, many mass lesions like frontal or temporal lobe meningiomas, low grade gliomas, mesencephalic cysts, primary CNS lymphomas, glioblastomas, astrocytomas and rarely sub dural hematomas and posterior fossa tumors may cause parkinsonism either by direct effect on basal ganglia or obstruction of CSF flow.,, These patients usually have other signs such as raised intracranial pressure. Rarely normal pressure hydrocephalus may be confused with PD due to abnormal gait. However, cognitive decline, urinary disturbances and sparing of upper limbs differentiate it from PD. Neuroimaging shows ventriculomegaly out of proportion to atrophy. Occasionally patients with hydrocephalus and raised pressure present with parkinsonism.
Psychogenic parkinsonism occurs rarely. The diagnosis of psychogenic parkinsonism is difficult due to marked heterogeneity of presentation of organic parkinsonism and lack of a confirmatory test for definite diagnosis. The differentiating features are same frequency of tremor at rest and postural tremor; tremor varies in frequency and rythmicity and may remit on distraction. Rigidity is variable and lessens on distraction. The gait is atypical with affected arm held tight to trunk and reactions to minimal displacement are bizarre. The symptoms are maximal at onset with early disability and absence of response to drugs. The psychiatric co-morbidities are depression; conversion disorders with features of multiple somatizations were present.
An enormous number of differential diagnoses as listed in this review, which can cause akinetic rigid syndrome. However idiopathic Parkinson's disease is generally differentiated easily from these by typical features and no further investigations may be necessary. In atypical cases the most common causes in adults are either vascular or drug induced. Neuroimaging and typical clinical picture helps in differentiating other degenerative diseases from Parkinson's disease. In children akinetic rigid syndromes are uncommon. Among various differentials drug induced akinetic rigid states are most common. Wilson's disease should be excluded in all cases by copper studies. In rest of the cases work up is suggested by history and examination. Even if patient has atypical features and secondary parkinsonism a trial of levodopa therapy is warranted in all cases.
|1||Quinn N. Parkinsonism-recognition and differential diagnosis. BMJ 1995;310:447-52.|
|2||Ahlskog JE. Diagnosis and differential diagnosis of Parkinson's disease and parkinsonism. Parkinsonism Relat Disord 2000;7: 63-70. |
|3||Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: A clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181-4.|
|4||Quinn NP, Husain FA. Parkinson's disease. Br Med J 1986;293:379-82.|
|5||Findley LJ, Koller WC. Essential tremor: A review. Neurology 1987;37:1194-7.|
|6||Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, et al . Association between early-onset Parkinson's disease and mutations in the parkin gene. N Engl J Med 2000;342: 1560-7.|
|7||Bannister R, Oppenheimer DR. Degenerative diseases of the nervous system associated with autonomic failure. Brain 1972;95:457-74.|
|8||Biggins CA, Boyd JL, Harrop FM, Madeley P, Mindham RH, Randall JI, et al . A controlled, longitudinal study of dementia in Parkinson's disease. J Neurol Neurosurg Psychiatry 1992;55:566-71.|
|9||Neef D, Walling AD. Dementia with Lewy bodies: An emerging disease. Am Fam Physician 2006;73:1223-9.|
|10||Louis ED, Klatka LA, Liu Y, Fahn S. Comparison of extrapyramidal features in 31 pathologically confirmed cases of diffuse Lewy body disease and 34 pathologically confirmed cases of Parkinson's disease. Neurology 1997;48:376-80.|
|11||Gupta P, Behari M. Cognitive impairment in extrapyramidal disorders. In : Early cognitive impairment; Dilemmas of an aging brain. Tripathi M, Mendiratta MM, editors. Saloni Printers: 2005. p. 525-40.|
|12||Kumar R, Bergron C, Lang AE. Secondary Parkinsonism. In : Parkinson's disease and movement disorders. Jankovic J, Tolosa E, editors. Lippincott, Williams and Wilkins: 2002. p. 199-211.|
|13||Wenning GK, Ben Shlomo Y, Magalhaes M, Daniel SE, Quinn NP. Clinical features and natural history of multiple system atrophy. An analysis of 100 cases. Brain 1994;117:835-45.|
|14||Robbins TW, James M, Lange KW, Owen AM, Quinn NP, Marsden CD. Cognitive performance in multiple system atrophy. Brain 1992;115:271-91. |
|15||Yamamoto T, Sakakibara R, Uchiyama T, Liu Z, Ito T, Awa Y, et al . When is Onuf's nucleus involved in multiple system atrophy? A sphincter electromyography study. J Neurol Neurosurg Psychiatry 2005;76:1645-8.|
|16||Schrag A, Good CD, Miszkiel K, Morris HR, Mathias CJ, Lees AJ, et al . Differentiation of atypical parkinsonian syndromes with routine MRI. Neurology 2000;54:697-702.|
|17||Watanabe H, Saito Y, Terao S, Ando T, Kachi T, Mukai E, et al . Progression and prognosis in multiple system atrophy: An analysis of 230 Japanese patients. Brain 2002;125:1070-83.|
|18||Poewe WH, Wenning GK. The natural history of Parkinson's disease. Ann Neurol 1998;44:S1-9.|
|19||Rampello L, Butta V, Raffaele R, Vecchio I, Battaglia G, Cormaci G, et al . Progressive supranuclear palsy: A systematic review. Neurobiol Dis 2005;20:179-86|
|20||Golbe LI, Davis PH, Schoenberg BS, Duvoisin RC. Prevalence and natural history of progressive supranuclear palsy. Neurology 1988;38:1031-4.|
|21||Maher ER, Smith EM, Lees AJ. Cognitive deficits in the Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). J Neurol Neurosurg Psychiatry 1985;48:1234-9.|
|22||Louis ED, Luchsinger JA. History of vascular disease and mild parkinsonian signs in community-dwelling elderly individuals. Arch Neurol 2006;63:717-22.|
|23||Sibon I, Tison F. Vascular parkinsonism. Curr Opin Neurol 2004;17:49-54.|
|24||Riley DE. Secondary Parkinsonism. In : Parkinson's disease and movement disorders. Jankovic J, Tolosa E, editors. Lippincott, Williams and Wilkins: 2002. p. 199-211.|
|25||Kitzberger R, Madl C, Ferenci P. Wilson disease. Metab Brain Dis 2005;20:295-302.|
|26||Sinha S, Jha DK, Sinha KK. Wilson's disease in Eastern India. J Assoc Physicians India 2001;49:881-4.|
|27||Hague SM, Klaffke S, Bandmann O. Neurodegenerative disorders: Parkinson's disease and Huntington's disease. J Neurol Neurosurg Psychiatry 2005;76:1058-63.|
|28||Gollomp SM. Rigid variant of Huntington's disease. In : Stern MB, Koller WC, editors. Parkinsonian syndromes. Marcel Dekker: New York; 1993. p. 111-22.|
|29||Adler CH. Differential diagnosis of Parkinson's disease. Med Clin North Am 1999;83:349-67.|
|30||Vinton A, Fahey MC, O'Brien TJ, Shaw J, Storey E, Gardner RJ, et al . Dentatorubral-pallidoluysian atrophy in three generations, with clinical courses from nearly asymptomatic elderly to severe juvenile, in an Australian family of Macedonian descent. Am J Med Genet A 2005;136:201-4.|
|31||Ragothaman M, Sarangmath N, Chaudhary S, Khare V, Mittal U, Sharma S, et al . Complex phenotypes in an Indian family with homozygous SCA2 mutations. Ann Neurol 2004;55:130-3.|
|32||Peppard RF, Lu CS, Chu NS, Teal P, Martin WR, Calne DB. Parkinsonism with neuroacanthocytosis. Can J Neurol Sci 1990;17:298-301.|
|33||Stephen PJ, Williamson J. Drug-induced parkinsonism in the elderly. Lancet 1984;2:1082-3.|
|34||Jankovic J. Tardive syndromes and other drug induced movement disorders. Clin Neuropharmachol 1995;18:197-214.|
|35||Hollander H, Golden J, Mendelson T, Cortland D. Extra pyramidal symptoms in AIDS patients given low-dose metoclopramide or chlorpromazine. Lancet 1985;2:1186.|
|36||Kirschberg GJ. Dyskinesia-An unusual reaction to ethosuximide. Arch Neurol 1975;32:137-8.|
|37||Lancman ME, Asconape JJ, Penry JK. Choreiform movements associated with the use of valproate. Arch Neurol 1994;51:702-4.|
|38||Lightman SL. Phenobarbital dyskinesia. Postgrad Med J 1978;54:114-5.|
|39||Walker JM, Matsumoto RR, Bowen WD, Gans DL, Jones KD, Walker FO. Evidence for a role of haloperidol-sensitive sigma-'opiate' receptors in the motor effects of antipsychotic drugs. Neurology 1988;38:961-5. |
|40||Bonuccelli U, Nocchiero A, Napolitano A, Paoletti AM, Melis GB, Corsini GU, et al . Domperidone-induced acute dystonia and polycystic ovary syndrome. Mov Disord 1991;6:79-81.|
|41||Romisher S, Felter R, Dougherty J. Tagamet-induced acute dystonia. Ann Emerg Med 1987;16:1162-4.|
|42||Perez Trullen JM, Modrego Pardo PJ, Vazquez Andre M, Lopez Lozano JJ. Bromazepam-induced dystonia. Biomed Pharmacother 1992;46:375-6.|
|43||Linazasoro G, Marti Masso JF, Olasagasti B. Acute dystonia induced by sulpiride. Clin Neuropharmacol 1991;14:463-4.|
|44||Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983;219:979-80.|
|45||Jiang YM, Mo XA, Du FQ, Fu X, Zhu XY, Gao HY, et al . Effective treatment of manganese-induced occupational parkinsonism with p-aminosalicylic acid: A case of 17-year follow-up study. J Occup Environ Med 2006;48:644-9.|
|46||Carella F, Grassi MP, Savoiardo M, Contri P, Rapuzzi B, Mangoni A. Dystonic-Parkinsonian syndrome after cyanide poisoning: Clinical and MRI findings. J Neurol Neurosurg Psychiatry 1988;51:1345-8.|
|47||Choi IS. Parkinsonism after carbon monoxide poisoning. Eur Neurol 2002;48:30-3. |
|48||Bitar ZI, Ashebu SD, Ahmed S. Methanol poisoning: Diagnosis and management. A case report. Int J Clin Pract 2004;58:1042-4.|
|49||Krauss JK, Mohadjer M, Wakhloo AK, Mundinger F. Dystonia and akinesia due to pallidoputaminal lesions after disulfiram intoxication. Mov Disord 1991;6:166-70.|
|50||Bhatt MH, Elias MA, Mankodi AK. Acute and reversible parkinsonism due to organophosphate pesticide intoxication: Five cases. Neurology 1999;52:1467-71.|
|51||Chen WX, Wang P, Yan SX, Li YM, Yu CH, Jiang LL. Acquired hepatocerebral degeneration: A case report. World J Gastroenterol 2005;11:764-6.|
|52||Panagariya A, Sureka RK, Udainiya DK. Parkinsonism and recovery in central and extrapontine myelinolysis. Neurol India 2005;53:219-20.|
|53||Bhatt MH, Obeso JA, Marsden CD. Time course of postanoxic akinetic-rigid and dystonic syndromes. Neurology 1993;43: 314-7.|
|54||Walker RH, Spiera H, Brin MF, Olanow CW. Parkinsonism associated with Sjogren's syndrome: Three cases and a review of the literature. Mov Disord 1999;14:262-8.|
|55||Golbe LI, Miller DC, Duvoisin RC. Paraneoplastic degeneration of the substantia nigra with dystonia and parkinsonism. Mov Disord 1989;4:147-52.|
|56||Asherson RA, Khamashta MA, Ordi-Ros J, Derksen RH, Machin SJ, Barquinero J, et al . The "primary" antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore) 1989;68:366-74.|
|57||Krusz JC, Koller WC, Ziegler DK. Historical review: Abnormal movements associated with epidemic encephalitis lethargica. Mov Disord 1987;2:137-41.|
|58||Nath A, Jankovic J, Pettigrew LC. Movement disorders and AIDS. Neurology 1987;37:37-41.|
|59||Garg RK. Subacute sclerosing panencephalitis. Postgrad Med J 2002;78:63-70.|
|60||DeBiasi RL, Solbrig MV, Tyler KL. Infections of the nervous system. In : Neurology in clinical practice. Bradley, et al , editors. Butterworth Heinmann: 2004. p. 1515-43.|
|61||Decaux G, Szyper M, Ectors M, Cornil A, Franken L. Central nervous system complications of Mycoplasma pneumoniae . J Neurol Neurosurg Psychiatry 1980;43:883-7.|
|62||Nath A, Hobson DE, Russell A. Movement disorders with cerebral toxoplasmosis and AIDS. Mov Disord 1993;8:107-12.|
|63||Prusiner SB. Shattuck lecture-Neurodegenerative diseases and prions. N Engl J Med 2001;344:1516-26.|
|64||Reik L, Steere AC, Bartenhagen NH, Shope RE, Malawista SE. Neurologic abnormalities of Lyme disease. Medicine (Baltimore) 1979;58:281-94.|
|65||Jones AL, Bouchier IA. A patient with neurosyphilis presenting as chorea. Scott Med J 1993;38:82-4.|
|66||Medley DR. Chorea and bacterial endocarditis. Br Med J 1963;1:861-2.|
|67||Bhatt M, Desai J, Mankodi A, Elias M, Wadia N. Posttraumatic akinetic-rigid syndrome resembling Parkinson's disease: A report on three patients. Mov Disord 2000;15:313-7.|
|68||Mendez MF. The neuropsychiatric aspects of boxing. Int J Psychiatry Med 1995;25:249-62.|
|69||Krauss JK, Paduch T, Mundinger F, Seeger W. Parkinsonism and rest tremor secondary to supratentorial tumours sparing the basal ganglia. Acta Neurochir (Wien) 1995;133:22-9.|
|70||Pohle T, Krauss JK. Parkinsonism in children resulting from mesencephalic tumors. Mov Disord 1999;14:842-6.|
|71||Krul JM, Wokke JH. Bilateral subdural hematoma presenting as subacute parkinsonism. Clin Neurol Neurosurg 1987;89:107-9.|
|72||Petersen RC, Mokri B, Laws ER Jr. Surgical treatment of idiopathic hydrocephalus in elderly patients. Neurology 1985;35:307-11.|
|73||Krauss JK, Regel JP, Droste DW, Orszagh M, Borremans JJ, Vach W. Movement disorders in adult hydrocephalus. Mov Disord 1997;12:53-60.|
|74||Lang AE, Koller WC, Fahn S. Psychogenic parkinsonism. Arch Neurol 1995;52:802-10.|
|75||Buchman AS, Goetz CG, Klawans HL. Hemiparkinsonism with hemiatrophy. Neurology 1988;38:527-30.|