Acute Parkinsonism

Maheen Kalwar (1), Syeda Zuhaa Hassan (2), Adeel Memon (3)
1 - Dow Medical College, Karachi, Pakistan.
2 - Dow Medical College, Karachi, Pakistan.
3 - Dow Medical College, Karachi, Pakistan


Introduction

  • Acute Parkinsonism (AP) is a relatively uncommon phenomenon, and has an abrupt onset of symptoms.
  • The signs and symptoms evolve over a period of a few hours to weeks.
  • Presents secondary to acute insults involving the Dopaminergic and Nigro-Striatal Pathway.
  • Common causes of AP include intake of certain drugs (medicinal and recreational), structural/vascular abnormalities, infections, psychiatric manifestations and autoimmune disorders

Etiology and Classification

  • Etiological classification of Acute Parkinsonism is multifactorial

Table 1. Etiological Classification of Acute Parkinsonism

Etiological Classification of Acute Parkinsonism
Etiology
Classification
Vascular (Acute/Subacute) Tumor (Hematoma, Aneurysm)
MPTP Carbon Monoxide
Catatonia Conversion disorder
Influenza A virus Human Immunodeficiency Virus (HIV) Japanese Encephalitis Virus (JEV) West Nile virus (WNV) Coxsackie virus Others

Structural lesions

  • Structural brain defects causing dysfunction of basal ganglia or their connections; most commonly of vascular origin.

Vascular Parkinsonism (VP) - Acute subtype

  • Acute (or subacute) form of VP most frequently occurs due to lacunar infarcts in basal ganglia.

Epidemiology

  • Acute (or subacute) form occurs in 20-25% of all the patients presenting with VP.
  • Majority of the affected individuals are over 65 years of age.

Risk Factors

  • Identical to risk factors causing the progressive subtype of VP.
💡
VP with an insidious onset is covered in Secondary Parkinsonism

Pathophysiology

  • Stroke (Ischemic>Hemorrhagic) in basal ganglia causing disruption of the nigrostriatal pathways.

Clinical Manifestations

  • Usually presents within 1-6 months of stroke occurrence; typically asymmetric presentation.
  • Overlapping features among the two subtypes include; gait and postural instability, cognitive decline, incontinence, and pseudobulbar palsy.
  • Resting tremor and upper motor neuron signs may or may not be present.
  • History might be suggestive of stroke, frequent falls and vascular risk factors.

Diagnosis

  • MRI can display contralateral hyperintense signals in substantia nigra, or along the nigrostriatal pathway.
  • Normal or symmetrically reduced binding on DaTscan (Dopamine transporter imaging), and preserved olfactory function may support the diagnosis.
☝️
According to one proposed criterion, a clinical diagnosis of acute VP can be made if;
  • Parkinsonism* occurs within a year after stroke, and
  • Lacunar infarcts in basal ganglia are evident on imaging, with positive clinical correlation.
* Parkinsonism is characterized by hypokinesia, in addition to one or more of the following; rigidity and postural instability.

Treatment

  • Levodopa has demonstrated significant improvement in symptoms.
  • The dose can be increased to up to 1000mg per day.
  • Antiplatelet therapy, physical exercise and control of risk factors may improve outcome.

Tumor

  • A vascular space-occupying mass, such as an aneurysm or a hematoma, may present with acute onset Parkinsonism.
  • Resection of the mass is the appropriate treatment.

Toxic/Metabolic

  • Features of Parkinsonism caused by exposure to certain toxins or metabolic disturbances within the body.
  • Common toxins include MPTP, Carbon Monoxide and Manganese.
  • Metabolic insults causing AP include central and extra pontine myelinolysis among other less common causes.

Carbon Monoxide (CO)

Epidemiology

  • Peaks in the 6th decade of life.
  • Both sexes are equally affected.

Pathophysiology

  • Although unclear, some studies suggest that parkinsonian features arise secondary to bilateral CO induced Globus pallidus lesions.

Clinical Manifestations

  • Post-exposure encephalopathy
  • Most patients present with Parkinsonian symptoms within 1 month of anoxic injury.
  • The most common symptoms include gait disturbances, urinary incontinence and delayed/slowed mentation.
  • Mutism
  • Signs such as bradykinesia, short stepping gait, rigidity and mask-like facies are also commonly observed.
  • Less common manifestations like grasp reflex, retropulsion and glabella sign may also be seen.
  • Although disequilibrium and intention tremors have been observed in some people, resting tremor is not seen.

Diagnosis

  • Approximately half of the patients show abnormal CT brain findings.
  • The most common findings include bilateral lesions in the Globus Pallidus as well as the cerebral cortex white matter.

Treatment

  • Most patients recover spontaneously over a period of 6 months or more.
  • Levodopa and anticholinergic therapy is not effective in the majority of cases.
  • Up till date only one case has been reported which showed an improvement on therapy with anticholinergics.

MPTP

Epidemiology

  • Initially identified by Langston et al in the San Francisco area as a cause of severe, acute-onset Parkinson's in intravenous drug abusers.
  • Not found naturally in the environment and is manufactured as a ‘synthetic heroin’.

Pathophysiology

  • MPTP is not toxic in itself, rather it crosses the blood brain barrier and is metabolised into MPP+.
  • MPP+ concentrates to toxic levels in the substantia nigra pars compacta and produces the symptoms seen.

Clinical manifestations

  • Resembles idiopathic PD more closely than any other cause of secondary/acute parkinsonism.
  • Presents with the classic bradykinesia, tremor and masked facies.
  • Lead pipe and cogwheel rigidity
  • Flexed posture
  • Loss of postural reflexes
☝️
Careful and detailed evaluation of patients is required as MPTP induced parkinsonism may be misdiagnosed as catatonic schizophrenia in some cases.

Diagnosis

  • Very similar to idiopathic PD in terms of both clinical manifestations and radiological findings.
  • Diagnosis is therefore made on the basis of acute symptom onset, temporal relationship of the symptoms to administration of the drug as well as a thorough history.

Treatment

  • Responds well to Levodopa.
☝️
Patients may start experiencing L-dopa-induced dyskinesia

Psychiatric

  • Parkinsonism due to psychogenic causes is uncommon.
  • Catatonia, conversion disorder and malingering are some of the causes associated with psychogenic parkinsonism.

Epidemiology

  • 2-5% of referrals to neurologists have a suspected psychogenic diagnosis.
  • More commonly seen in females.
  • Age range between 30-50 years.

Pathophysiology

  • Studies suggest that catatonia occurs secondary to NMDA hyperactivity which in turn leads to problems in GABA-A functioning.
  • Conversion disorder includes translation of mental stress into physical symptoms.

Risk factors

  • Previous history of a psychiatric illness
  • History of rape or other types of sexual abuse
  • Traumatic life events
  • Major surgery

Clinical features and Diagnosis

Table 2 details the clinical features and criteria involved in diagnosing psychogenic parkinsonism

notion image
Modified: Hinson, V. K., & Haren, W. B. (2006). Psychogenic movement disorders. The Lancet Neurology, 5(8), 695–700. https://doi.org/10.1016/s1474-4422(06)70523-3

Para-infectious

  • Neuronal loss (basal ganglia and its projections) due to neuro-inflammatory processes triggered by infectious agents.
  • Typically as a consequence of a viral illness.

Influenza A virus

Epidemiology

  • The 1918 Influenza Pandemic led to the discovery of Influenza-associated disease patterns with features of Parkinsonism, and a younger age of onset (20s-30s).
  • Von Economo described them as Encephalitis Lethargica (EL) and its sequela, Post-Encephalitic Parkinsonism (PEP).
  • Infecting more than 1 million people during the EL epidemic, it has become extremely rare since the past seven decades.

Pathophysiology

  • Progressive neuroinflammation, including meninges, and petechial hemorrhages in the Cortex, Brainstem and Spinal Cord in EL.
  • Loss of dopaminergic neurons in Substantia Nigra pars Compacta and presence of neurofibrillary tangles, without Lewy body deposition, in PEP.

Clinical Manifestations

  • Features may be similar to PD, or clinically different.
  • The table (Table 3) below describes them in detail.
 

Table 3. Clinical findings associated with EL and PEP

 

Risk factors

  • Recurrent Influenza attacks

Diagnosis

  • Diagnosis of exclusion.
  • Clinical history and presentation of the disease may help.
  • EL may precede PEP, unlike PD.

Treatment

  • Symptomatic treatment mainly.
  • Levodopa may display improvement in some patients.

Human Immunodeficiency Virus (HIV)

Epidemiology

  • About 5% of HIV infected individuals are reported to have Parkinsonism.
  • Usually in patients with CD4 T-cell count less than 40 cells/mm3.
  • Evidence of movement disorder symptoms has been displayed by a further 5-50% of patients suffering from AIDS.
  • Occurs commonly in a younger age group than PD (<60 years).

Pathophysiology

  • HIV may cause Parkinsonism as an early event due to viral infection, or in conjunction with AIDS Dementia Complex (ADC) late in the disease course.
  • Inflammation in the glial tissue encompassing basal ganglia, resulting in neuronal damage and death.
  • Alpha synuclein is also increasingly found in substantia nigra.

Clinical manifestations

  • Early-onset symmetrical Parkinsonism (predominantly motor), and gait involvement, with rapid deterioration of motor symptoms.
  • Resting tremor is absent.
  • ADC presents with facial masking and tremor, in addition to Parkinsonism.
  • Cognitive abnormalities and neuropsychiatric complications are also common in ADC.

Risk factors

  • Severe immunosuppression (CD4 T-cell count <40mm).

Diagnosis

  • DIP must be ruled out in patients with AIDS.
  • CT/MRI reveal calcified lesions in basal ganglia, hypertrophy of Putamen, and hypodense striatal lesions.
  • Increased metabolism in basal ganglia, and decreased overall cerebral metabolism correspond to the early and late changes on PET, respectively.

Treatment

  • Highly active antiretroviral therapy (HAART) is curative.
  • Simultaneously prescribed Levodopa may also show improvement.

Japanese Encephalitis Virus (JEV), West Nile Virus (WNV), and Coxsackie virus

  • Other viruses identified as probable causes of Parkinsonism (Table 4)

Table 4. Clinical Manifestations and Treatment of Parkinsonism caused by JEV, WNV, and Coxsackie virus

Other agents reported to cause PEP

  • Viral: Epstein Barr Virus, Varicella Zoster Virus, Hepatitis C Virus.
  • Bacteria: Helicobacter Pylori, Nocardia species, and Mycoplasma species.
  • Parkinsonism following Measles vaccine.

Autoimmune disorders

  • Parkinsonism is rare, but may accompany either systemic or localized autoimmune diseases.
  • They usually do not respond well to Levodopa.
  • Symmetrical onset is common.
☝️
Autoimmune disorders other than SLE may or may not have an acute onset. They are discussed in Secondary Parkinsonism.

Systemic Lupus Erythematosus (SLE)

Epidemiology

  • 1% of patients afflicted with SLE display symptoms of movement disorders.
  • Parkinsonism is a rare manifestation of NPSLE (Neuro-Psychiatric SLE).
  • Presents in children as well as adults.
  • More prevalent in females, with an onset in the early adulthood.

Pathophysiology

  • Vasculitis leading to hypoperfusion, specifically around substantia nigra.
  • Antibodies against dopaminergic neurons in serum, and anti-ribosomal-P protein found in serum as well as CSF, favor immune-mediated pathology.

Clinical Manifestations

  • Bradykinesia, tremor, rigidity, and hypomimic facies are among the most common features.
  • A few patients may present with only unilateral symptoms.
  • Mutism, psychosis and seizures are more commonly seen with juvenile SLE.
  • The chart below represents other neurologic and psychiatric symptoms observed in SLE.
 
notion image
Source: Barba, C., & Alexopoulos, H. (2019). Parkinsonism in autoimmune diseases. International Review of Neurobiology, 419–452. https://doi.org/10.1016/bs.irn.2019.10.015
 

Diagnosis

  • MRI shows enhancement of periventricular, frontal and parietal white matter regions, mainly on T2-weighted images.
  • Less frequently, ventricular enlargement, atrophy of cortex and infarction can also be seen on MRI.
  • SPECT (Single-Photon Emission Computed Tomography) may display altered cerebral perfusion; decreased around basal ganglia and biparietal areas, or increased supply to basal ganglia in the remaining few.
  • Increased protein, cells, and presence of anti-dopamine antibodies in CSF.

Treatment

  • Initial: high dose (pulse) steroids and immunosuppressive (cyclophosphamide) therapy.
  • Immunomodulatory agents such as intravenous immunoglobulin, plasmapheresis and rituximab may be effective.
  • Levodopa may be used in combination but the symptoms usually resolve without it.

Further reading

  1. Almajali M, Almajali F, Kafaie J, Chand P. Successful Utilization of Levodopa in HIV-Induced Parkinsonism. Cureus. 2020;12(12):e11825. Published 2020 Dec 1. doi:10.7759/cureus.11825
  1. Jang H, Boltz DA, Webster RG, Smeyne RJ. Viral parkinsonism. Biochim Biophys Acta. 2009;1792(7):714-721. doi:10.1016/j.bbadis.2008.08.001
  1. Moraes de Moraes MP, Salomão RPA, Felício AC, Abrantes FF, Barsottini OGP, Pedroso JL. Reversible Acute Parkinsonism and Unusual Neuroimaging Findings in Systemic Lupus Erythematosus. Mov Disord Clin Pract. 2020;7(4):459-461. Published 2020 Apr 7. doi:10.1002/mdc3.12943

Bibliography

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  1. Langston JW. The MPTP Story. J Parkinsons Dis. 2017;7(s1):S11-S19. doi:10.3233/JPD-179006
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  1. Hinson VK, Haren WB. Psychogenic movement disorders. Lancet Neurol. 2006;5(8):695-700. doi:10.1016/S1474-4422(06)70523-3
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  1. Limphaibool N, Iwanowski P, Holstad MJV, Kobylarek D, Kozubski W. Infectious Etiologies of Parkinsonism: Pathomechanisms and Clinical Implications. Front Neurol. 2019;10:652. Published 2019 Jun 19. doi:10.3389/fneur.2019.00652
  1. Jang H, Boltz DA, Webster RG, Smeyne RJ. Viral parkinsonism. Biochim Biophys Acta. 2009;1792(7):714-721. doi:10.1016/j.bbadis.2008.08.001
  1. Tse W, Cersosimo MG, Gracies JM, Morgello S, Olanow CW, Koller W. Movement disorders and AIDS: a review. Parkinsonism Relat Disord. 2004;10(6):323-334. doi:10.1016/j.parkreldis.2004.03.001
  1. Tadokoro K, Ohta Y, Sato K, et al. A Japanese Encephalitis Patient Presenting with Parkinsonism with Corresponding Laterality of Magnetic Resonance and Dopamine Transporter Imaging Findings. Intern Med. 2018;57(15):2243-2246. doi:10.2169/internalmedicine.0337-17
  1. Chayasak Wantaneeyawong, Nuntana Kasitanon, Kullanit Kumchana & Worawit Louthrenoo (2020) Acute parkinsonism in patients with systemic lupus erythematosus: a case report and review of the literature, International Journal of Neuroscience, DOI: 10.1080/00207454.2020.1847106
  1. Barba C, Alexopoulos H. Parkinsonism in autoimmune diseases. Int Rev Neurobiol. 2019;149:419-452. doi:10.1016/bs.irn.2019.10.015
  1. Tan EK, Chan LL, Auchus AP. Reversible parkinsonism in systemic lupus erythematosus. J Neurol Sci. 2001;193(1):53-57. doi:10.1016/s0022-510x(01)00604-9
 
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